Process of Fluorinating Inorganic or Organic Compounds by Direct Fluorination

ABSTRACT

The invention relates to a use of a fluorination gas, and the elemental fluorine (F2) is present in a high concentration, for example, in a concentration of elemental fluorine (F2), especially of equal to much higher than 15 or even 20% by volume, and to a process for the manufacture of a fluorinated compound by direct fluorination employing a fluorination gas, wherein the elemental fluorine (F2) is present in a high concentration. The process of the invention is directed to the manufacture of a fluorinated compound, for the exception of fluorinated benzene, by direct fluorination. Especially the invention is of interest in the preparation of fluorinated organic compounds, final products and as well intermediates, for usage in agro-, pharma-, electronics-, catalyst, solvent and other functional chemical applications. The fluorination process of the invention may be performed batch-wise or in a continuous manner.

BACKGROUND OF THE INVENTION Field of the Disclosure

The invention relates to process for the manufacture or preparation offluorinated inorganic or organic compounds, respectively, using afluorination gas comprising elemental fluorine (F₂). The process of theinvention, for example, can comprise a batch or continuous manufactureor preparation of fluorinated inorganic or organic compounds,respectively, using fluorination gas comprising elemental fluorine (F₂).

Description of Related Art

Fluorinated organic compounds in industrial scale are prepared byfluorine halogen exchange using anhydrous HF, addition of HF to olefinicdouble bonds, fluorinating agents like amine×nHF, electrofluorinationwith HF (in situ generation of F₂) where in latter case selectivity,scalability and missing environmental friendliness (formation of verytoxic partial fluorinated compounds) often is and remains an unsolvedproblem. Another existing fluorination procedure is using F₂-gasdirectly. But this requires—besides availability of industrialquantities—the very skilled handling of F₂-gas and co-produced HF(hydrogen (H) vs. fluorine (F) exchange reaction).

Elemental fluorine (F₂) is a yellow compressed gas (fluorine gas,F₂-gas) with a pungent odor; it is a strong oxidant, reacts violentlywith combustible and reducing substances. Due to its strong chemicalactivity, and therefore, the need of equipment and containers withstrong corrosion resistance to fluorine and HF, F₂-gas is usually mixedwith nitrogen (N₂). In Europe, usually only mixtures of 95% N2 with only5% F₂-gas are allowed to be transported, or with exemption permissiononly of up to 10% content of F₂-gas.

In Asia, a ratio up to 20% F₂-gas in inert gas like N₂ is available.

Such dilution of F₂-gas by inert gas like N₂ is necessary because ofsafety and reducing and/or controlling the chemical activity orreactivity of F₂-gas in chemical reactions. However, this dilution ofF₂-gas by inert gas needed for the said reason of “deactivation” inindustrial scale has the disadvantage that on the one side the dosing ofF₂-gas diluted by inert gas is very challenging, and on the other sideeven more important as drawback, that the heat transfer in reactorequipment during chemical reactions with F₂-gas, as these reaction arevery exothermic, is very much reduced by inert gas, and due to thediluting inert gas is resulting in reduced heat transfer, and in worstcase might even cause runaways. Hence, in principle the inert gas isundesirably functioning as insulation gas.

Meinert H., has reported about some reaction, and observeddecomposition, of fluorine with pyridine at temperatures of −40° C. or−80° C. of fluorine diluted by nitrogen (ZeitschriftfürChemie, Leipzig,DeutscherVerlagfürGrundstoffindustrie, 1961-1990, ISSN 0044-2402, 1965,Volume 5 (2). Comments, Page 64, ZCM 1130 received on 7 Dec. 1964).Roger S. et al. have reported some reactions of CF₃OF(trifluoromethylhypofluorite (Journal of the American Chemical SocietyVolume 79, 1957, 5625-5627). The document EP 0267627 A1 (Ausimont)describes a process for the preparation of halogenated polyethers, ande.g., is using CF₃OF (trifluoromethylhypofluorite.

It is known in the prior art to fluorinate deactivated benzenederivatives with a diluted fluorination gas, e.g., in Chambers et al.(Journal of Fluorine Chemistry 128 (2007) 29-33). Chambers is using as afluorination gas containing 10% (vol.-%) elemental fluorine (F₂) innitrogen (N2) as inert gas, and is using solvents for the reaction,e.g., acetonitrile or formic acid reaction media. Chambers is reportingrepresentative direct fluorination reactions of 1,4-disubstitutedaromatic systems bearing an electron withdrawing and releasing group,using microreactor technology. The fluorinated products are obtained bya process consistent with an electrophilic substitution process due tothe solvents used. Thus, high selectivity and yields of monofluorinatedproducts are reported by Chambers when using either acetonitrile orformic acid reaction media. It is known in the prior art that highrelative permittivity solvents or protonic acids can be used veryeffectively for the fluorination of aromatic systems because, in thesemedia, the fluorine molecule is rendered more susceptible towardsnucleophilic attack by interaction with the solvent while competing freeradical processes are minimized. However, in the process described byChambers, typically, reactions are carried out only in small scalereactions, for example over a 16 h period enabling 5 to 10 g of crudeproduct to be collected.

Also, Chambers tested in the same experimental setting as described hereabove, the direct fluorination of aromatic rings bearing two strongelectron withdrawing groups, which aromatic rings are, of course,relatively unreactive towards electrophilic attack. However, reactionsbetween such substrates and elemental fluorine (F₂), i.e., using thefluorination gas containing 10% (vol.-%) elemental fluorine (F₂) innitrogen (N2) as inert gas, and using a microreactor gave lowconversions to fluorinated products, but in very selective, cleanreactions. Nevertheless, also in this process described by Chambers,typically, reactions are carried out only in small scale reactions, forexample over a 16 h period enabling 5 to 10 g of crude product to becollected.

Importantly, it must be noted that despite the successful conversions inthe range of 78% to 91% of fluorination reactions on deactivated benzenederivatives with a diluted fluorination gas in acetonitrile as solvent,nevertheless Chambers did not test, and neither motivate for testing ofnon-deactivated benzene itself, nor any other (aromatic or non-aromatic)organic compound or any inorganic compound, neither in small-scale of 5to 10 g product quantities nor in large-scale at all.

Accordingly, there is a high demand of enabling large-scale and/orindustrial production of fluorinated inorganic compounds or organiccompounds, respectively, by directly fluorinating an inorganic startingcompound or organic starting compound, respectively, in a controlled andeffective manner in a large-scale and/or industrial setting.

When producing fluorinated inorganic compounds or organic compounds,respectively, by directly fluorinating an inorganic starting compound ororganic starting compound, respectively, in a controlled and effectivemanner, in another aspect it is also desired to minimize, or even tosubstantially avoid, the dilution of the elemental fluorine (F₂) byinert gas, e.g. by nitrogen (N2) as inert gas, and at least to enablethe use of fluorination gas containing essentially higher concentratedelemental fluorine (F₂) than those concentrations described above andused in the prior art, e.g., essentially higher concentrated elementalfluorine (F₂) than 10% by volume as used by Chambers or available underexemption in Europe, or essentially higher concentrated elementalfluorine (F₂) than 20% by volume as available Asia.

It is an object of the present invention to provide a high efficientprocess for the manufacture or for preparation of fluorinated inorganiccompounds or organic compounds, respectively, by direct fluorinationusing fluorine gas (F₂), wherein in the fluorination process a fluorinegas (fluorination gas) with concentrations of substantially more than,in particular very much higher than 15 or even 20% by volume ofelemental fluorine (F₂), especially of equal to much higher than 25% byvolume (i.e., at least 25% by volume) of elemental fluorine (F₂),preferably of equal to much higher than 35 or even 45% by volume ofelemental fluorine (F₂), can be used for chemical synthesis, especiallyfor the manufacture or for preparation of fluorinated inorganiccompounds or fluorinated organic compounds, respectively, as finalproducts and/or intermediates, for usage in agro-, pharma-,electronics-, catalyst, solvent and other functional chemicalapplications.

It is preferably an object of the present invention to provide afluorination process for the manufacture or preparation of fluorinatedinorganic compounds or fluorinated organic compounds, respectively, bydirect fluorination using fluorine gas (F₂), by which it is possible toperform chemistry with a fluorination gas consisting essentially ofF₂-gas as it directly comes out of the F₂-electrolysis reactors(fluorine cells), optionally only diluted for a minor degree, e.g., foradapting and controlling the fluorination process and its parameters.

It is preferably another object of the present invention to provide afluorination process for the manufacture or preparation of fluorinatedinorganic compounds or fluorinated organic compounds, respectively, bydirect fluorination using fluorine gas (F₂-gas), by means of specialequipment and special reactor design.

It is preferably still another object of the present invention toprovide a fluorination process for the manufacture or preparation offluorinated inorganic compounds or fluorinated organic compounds,respectively, by direct fluorination using fluorine gas (F₂-gas),wherein the process can be performed in a large-scale and/or industrialproduction of fluorinated inorganic compounds or organic compounds.

SUMMARY OF THE INVENTION

The objects of the invention are solved as defined in the claims, anddescribed herein after in detail.

Regarding the scope of the present invention it is to be noted that,that for legal reason only but not for technical reason, there is aproviso that the organic starting compound, to be reacted with thefluorination gas, is not benzene, not benzoic acid, and not a benzoicacid derivative, and the fluorinated organic compound produced is not afluorinated benzene, and in particular the fluorinated compound producedis not monofluorobenzene.

According to the objects, the present invention provides a highefficient process for the manufacture or for preparation of afluorinated inorganic compound or fluorinated organic compound,respectively, by direct fluorination using fluorine gas (F₂), wherein inthe fluorination process a fluorine gas (fluorination gas) withconcentrations of substantially more than, in particular very muchhigher than 15% by volume or in particular than 20% by volume ofelemental fluorine (F₂), especially of equal to much higher than 25% byvolume (i.e., at least 25% by volume) of elemental fluorine (F₂),preferably of equal to much higher than 35% by volume or in particularthan 45% by volume of elemental fluorine (F₂), is used for chemicalsynthesis, especially for the manufacture or for preparation of afluorinated inorganic compound or fluorinated organic compound,respectively, as final products and/or intermediates, for usage inagro-, pharma-, electronics-, catalyst, solvent and other functionalchemical applications.

Preferably, the present invention provides a fluorination process forthe manufacture or preparation of a fluorinated inorganic compound orfluorinated organic compound, respectively, by direct fluorination usingfluorine gas (F₂), by which it is possible to perform chemistry with F₂as it comes directly out of the F₂-electrolysis reactors (fluorinecells).

More preferably, the present invention provides a fluorination processfor the manufacture or preparation of a fluorinated inorganic compoundor fluorinated organic compound, respectively, by direct fluorinationusing fluorine gas (F₂), by means of special equipment and specialreactor design, for example, as described in FIG. 1 and FIG. 2hereunder. The special equipment and special reactor design employed bythe invention may comprise one or more packed bed towers, e.g., in theform of a gas scrubber system, or one or more microreactors. A packedbed towers, e.g., in the form of a gas scrubber system, may bepreferred, more preferably a packed bed towers, e.g., in the form of aninverse gas scrubber system, used in a batch process as reactor.

The fluorination process for the manufacture or preparation of afluorinated inorganic compound or fluorinated organic compound,respectively, by direct fluorination using fluorine gas (F₂), can beperformed at suitable pressures, for examples at a pressure in the rangeof about 1 to about 25 bar (absolute), preferably at a pressure in arange of about 5 to about 20 bar (absolute), more preferably at apressure in a range of about 10 to about 20 bar (absolute), and morepreferably at a pressure in a range of about 15 to about 20 bar(absolute). In an example, the process is performed at a pressure ofabout 20 bar (absolute).

The fluorination process for the manufacture or preparation of afluorinated inorganic compound or fluorinated organic compound,respectively, by direct fluorination using fluorine gas (F₂), can beperformed at an approximately equimolar ratio of the inorganic startingcompound or the organic starting compound, respectively, to thefluorination gas comprising highly concentrated F₂-gas. Preferably, thereaction is performed with a slight molar excess amount of thefluorination gas comprising highly concentrated F₂-gas.

Further, it has been discovered that despite the exothermic character ofthe direct fluorination reaction, e.g., within a given time period(e.g., less than 10 hours, or even less than 5 hours), the reaction ofthe invention can be performed as a larger scale reaction with highconversion rates, and without major impurities in the resultingfluorinated product. The fluorinated product can be produced in kilogramscale quantities, e.g., the direct fluorination process of the inventioncan be performed in a large-scale and/or industrial production of afluorinated inorganic compound or fluorinated organic compound,respectively. For reason of calculating quantities, as an example butnot intended to be limiting, reference is made to the larger scalereaction with high conversion rates of some example inorganic startingcompounds or organic starting compounds, respectively; and resultingfluorinated inorganic compounds or fluorinated organic compounds,respectively; as displayed in the following table:

Example Quantity Kg (mol) Reaction Time (h) Yield (%) Kg/h (mol/h)Reactor Type 1 4.0 (97.4 mol) 5 96 0.8 (97.4 mol/h) Column/Batch 2 0.234(5.7 mol) 1 96 0.234 (5.7 mol/h) Microreactor/Continuous 7 0.017 (1 mol)0.017 (1 mol/h) Microreactor/Continuous 11 0.200 (1.51 mol) 1 94 0.200(1.51 mol/h) Microreactor/Continuous 13 0.4707 (2.8 mol) 1 89 0.4707(2.8 mol/h) Microreactor/Continuous 14 0.3999 (2.7 mol) 1 79 0.3999 (2.7mol/h) Microreactor/Continuous

Accordingly, it is preferred that the direct fluorination process of theinvention is performed in a large-scale and/or industrial production ofa fluorinated inorganic compound or fluorinated organic compound,respectively, e.g., in kilogram scale quantities, wherein in a batchprocess, or optionally in a continuous process, in a column reactor asdescribed herein, e.g., in a time period of 1 h, at least about 0.1 kgof starting compound is fluorinated per hour, preferably at least about0.3 kg or at least about 0.5 kg of starting compound, more preferably atleast about 0.75 kg of starting compound, is fluorinated per hour, toyield a fluorinated inorganic compound or fluorinated organic compound,respectively, with a conversion of at least 75%, preferably about 80%conversion, more preferably about 85% conversion, and even morepreferably about 95% conversion.

Accordingly, it is preferred that the direct fluorination process of theinvention is performed in a large-scale and/or industrial production ofa fluorinated inorganic compound or fluorinated organic compound,respectively, e.g., in a larger scale or even kilogram scale quantities,wherein in a microreactor process, in a continuous process, as describedherein, e.g., in a time period of 1 h, at least about 0.5 mol/h startingcompound, or at least about 1 mol/h starting compound, preferably atleast about 1.5 mol/h starting compound, more preferably at least about2 mol/h starting compound, even more preferably at least about 2.5 mol/hof starting compound, is fluorinated for a desired period of time (e.g.,of at least 0.5 h, preferably of at least 1 h, more preferably of atleast 2, 3, 4 or 5 h) to produce the required large-scale and/orindustrial scale quantity of a fluorinated inorganic compound orfluorinated organic compound, respectively, a fluorinated inorganiccompound or fluorinated organic compound, respectively, with aconversion of at least 75%, preferably about 80% conversion, morepreferably about 85% conversion, and even more preferably about 95%conversion.

In a particular embodiment, it is preferred that the direct fluorinationprocess of the invention is performed in a large-scale and/or industrialproduction of a fluorinated inorganic compound or fluorinated organiccompound, respectively, e.g., in kilogram scale quantities, wherein in amicroreactor process, in a continuous process, as described herein, thestarting material, i.e., the inorganic starting compound or organicstarting compound, respectively, is fluorinated for a desired period oftime of at least about 1 h, preferably of at least about 2 h, morepreferably of at least about 3 h, even more preferably of at least about4 h, or most more preferably of at least about 5 h, or for even a longertime period that 5 h, to produce the required large-scale and/orindustrial scale quantity of a fluorinated inorganic compound orfluorinated organic compound, respectively, with a conversion of atleast 75%, preferably about 80% conversion, more preferably about 85%conversion, and even more preferably about 95% conversion.

Hence, in the said direct fluorination process of the inventionperformed in a large-scale and/or industrial production of a fluorinatedinorganic compound or organic compound in a microreactor in a continuousprocess within e.g., in a time period of 1 h, approximate kilogram scalequantities of the starting material, i.e. an inorganic starting compoundor organic starting compound, respectively, of at least about 0.015 kgor about 0.05 kg or about 0.1 kg or about 0.2 kg or about 0.3 kg, or ofat least about 0.4 kg, or of at least about 0.5 kg, are fluorinated bydirect fluorination according to the invention, to produce the requiredlarge-scale and/or industrial scale quantity of a fluorinated inorganiccompound or fluorinated organic compound, respectively, with aconversion of at least 75%, preferably about 80% conversion, morepreferably about 85% conversion, and even more preferably about 95%conversion.

The reaction is performed with an equimolar amount of highlyconcentrated F₂-gas, and, except for the reactions with deactivatedbenzene derivatives (see Examples 13 and 14; see further below),preferably in a slight molar excess amount of about 0.01 to about 0.5mol/h, preferably of about 0.01 to about 0.4 mol/h or about 0.01 toabout 0.3 mol/h, more preferably of about 0.01 to about 0.2 mol/h, mostpreferably of about 0.01 to about 0.1 mol/h, of highly concentratedF₂-gas.

If the fluorination is carried out in a solvent, then the directfluorination according to the invention can be advantageously alsoperformed using slightly sub-molar amounts of the fluorination gascomprising highly concentrated F₂-gas. This is particularly the casewhen deactivated benzene derivatives are used as the starting compound,as further described below.

The invention also relates to a use of a fluorination gas, whereinelemental fluorine (F₂) is present in a high concentration ofsubstantially more than, in particular very much more than 15% by volumeor in particular than 20% by volume, preferably equal to or more than25% by volume (vol.-%), for the manufacture of a fluorinated inorganiccompound or fluorinated organic compound, respectively, in a liquidmedium comprising or consisting of an inorganic starting compound or anorganic starting compound, respectively, wherein in the staring compoundone or more hydrogen atoms are capable of being substituted by means ofa halogenation reaction, preferably wherein the fluorine (F₂) is presentin the fluorine containing gas in a high concentration in a range offrom substantially more than, in particular very much more than 15 or 20by volume (vol.-%) and up to 100% by volume, preferably equal to or morethan 25 by volume (vol.-%) and up to 100% by volume (vol.-%); with aproviso that the starting compound, to be reacted with the fluorinationgas, is not benzene, not benzoic acid, and not a benzoic acidderivative, and the fluorinated compound produced is not a fluorinatedbenzene, and in particular the fluorinated compound produced is notfluorobenzene or monofluorbenzene.

It is noted that the fluorination reaction of the present invention, inparticular when carried out in the specific and/or preferred equipmentor reactor designs as described by the present invention herein, can bealready performed with concentrations of elemental fluorine (F₂) of 15%by volume or in particular than 20% by volume.

However, it is preferred that the fluorination reaction of the presentinvention, also when carried out in the specific and/or preferredequipment or reactor designs as described by the present inventionherein, is performed with concentrations of elemental fluorine (F₂) atleast 25% by volume, and more preferably with concentrations ofelemental fluorine (F₂) of substantially more than 35% by volume or inparticular substantially more than 45% by volume of elemental fluorine(F₂).

According to the present invention it is particularly preferred toperform the fluorination process for the manufacture or preparation of afluorinated inorganic compound or fluorinated organic compound,respectively, by direct fluorination using fluorine gas (F₂), by whichcomes directly out of the F₂-electrolysis reactors (fluorine cells).Such electrolysis fluorine gas (F₂) normally has a concentration ofabout 97% elemental fluorine (F₂).

The electrolysis fluorine gas (F₂) normally having a concentration ofabout 97% elemental fluorine (F₂) can be used without purification as itis derived from the F₂-electrolysis reactors (fluorine cells), or ifdesired, it may be purified.

Further, the electrolysis fluorine gas (F₂) normally having aconcentration of about 97% by volume (vol.-%) of elemental fluorine (F₂)can be used in the in the such concentration as it is derived from theF₂-electrolysis reactors (fluorine cells), or optionally it may bediluted by an inert gas, preferably nitrogen (N₂), to a desiredconcentration of at least 80% by volume (vol.-%) of elemental fluorine(F₂). More preferably the electrolysis fluorine gas (F₂) is onlydiluted, if desired, by no more than 15% by volume (vol.-%), no morethan 10% by volume (vol.-%), and most preferably by no more that 5% byvolume (vol.-%), of an inert gas, preferably nitrogen (N₂).

Surprisingly it was also found that the use of inert gas in largerratios of inert gas to elemental fluorine has disadvantages in terms ofprocess controllability of the fluorination reaction, for example, interms of effective mixing of the elemental fluorine with the liquidcompound to be fluorinated, heat transfer control, e.g., poor heatexchange, and maintenance of desired reaction conditions in themicro-environments in the reaction mixture. These disadvantages equallyapply in bed tower reactor (gas scrubber system) technology and inmicrobubble microreactor or comparable continuous flow technology. Forexample, in a coil reactor or microreactor, at high inert gasconcentrations, e.g., low fluorine (F2) concentrations, in addition tothe poor heat exchange, there are also ineffective (reaction) zones with(inert) gas bubbles, which nullifies the advantages of using a coilreactor or a microreactor, and the same is observed in bed tower reactor(gas scrubber system) technology.

Definitions

Direct Fluorination: Introducing one or more fluorine atoms into acompound by chemically reacting a starting compound, e.g. according tothe present invention an inorganic starting compound or organic startingcompound, respectively, with elemental fluorine (F₂) such that one ormore fluorine atoms are covalently bound into the fluorinated inorganiccompound or organic compound, respectively.

Compound: A molecule composed of at least two atoms bound by covalentbinding. In the molecule, often also called substance, the atoms arecovalently linked together to form a self-contained, chemical formation.A molecule defined in this way is the smallest particle of a certainpure substance and has a determinable molecular mass, wherein the atomsare held together by chemical bonds and are at least as long stable thatthey can be observed, for example, at least spectroscopically. Amolecule or substance defined in this way is the smallest part of acertain pure substance and has a determinable molecular mass, and otherdeterminable physiochemical properties. Here, in the invention, forexample, the starting compound is a compound provided to be reacted withelemental fluorine (F₂). The starting compound may be an inorganicmolecule (i.e. no salt) as inorganic starting compound, or an organiccompound, respectively. The compound obtained by the process of theinvention, for example, may be a fluorinated inorganic compound or afluorinated organic compound, respectively. However, for the purpose ofthis invention, benzene is expressively excluded from the group oforganic starting compounds, and fluorinated benzene, fluorobenzene ormonofluorobenzene is expressively excluded from the group of fluorinatedorganic compounds to be produced.

Inorganic Chemistry is the chemistry of all carbon-free compounds andsome exceptions, i.e., it is the chemistry related to inorganicsubstances or inorganic compounds. Inorganic substances or compoundstraditionally include the elements and all compounds that do not containcarbon. There are some exceptions to carbon compounds, which are builtup just like typical inorganic substances or historically assigned toinorganic compounds. These include the hydrogen-free chalcogenides ofcarbon (carbon monoxide, carbon dioxide, carbondisulfide), carbonic acidand carbonates, carbides and ionic cyanides, cyanates and thiocyanates.The hydrocyanic acid is considered a borderline case and is treated bothin the organic and inorganic. Although traditionally classified asinorganic chemistry, it may be considered to be a nitrile (organicgroup) of formic acid.

Organic chemistry (organics) is a branch of chemistry which covers thechemical compounds based on carbon, with some exceptions such as someinorganic carbon compounds and elemental (pure) carbon; see for examplealso here before exceptions and borderline cases mentioned in thedescription of inorganic chemistry. With few exceptions, organicchemistry encompasses the chemistry of all compounds that carbon entersinto with itself and other elements. This also includes all the buildingblocks of the currently known life. The exceptions formally concernfirst the elemental forms of carbon (graphite, diamond) and,systematically, all non-hydrogen-containing chalcogenides of carbon(carbon monoxide, carbon dioxide, carbondisulfide), carbonic acid andcarbonates, carbides and ionic cyanides, cyanates and thiocyanates (seecarbon compounds).

Hydrocyanic acid belongs to the borderland of inorganic and organicchemistry. Although traditionally classified as inorganic chemistry, itis considered to be a nitrile (organic group) of formic acid. Thecyanides are treated in the inorganic, which here only the salts ofhydrogen cyanide are meant, whereas the esters of hydrocyanic acid knownunder the same name belong as nitriles to the organics. The cyanicacids, thiocyanic acids and their esters are also considered asborderline cases.

Further, the organometallic chemistry (metal organyls) is notspecifically attributed to organic or inorganic chemistry. In thecontext of the present invention, organometallic chemistry (metalorganyls) is not encompassed by the meanings of both, the organicchemistry or inorganic chemistry, or by the meaning of organic compoundor inorganic compound.

The term “deactivated benzene derivative” denotes a substituted benzene(C6-aromatic systems) bearing an electron withdrawing and releasinggroup. For example, such deactivating group (an electron withdrawing andreleasing group) can be a nitro group (NO₂), a nitrile group (CN), ahydroxyl group (OH), an O-methyl group (OCH₃), an aldehyde group (CHO).There may be one to three of such deactivating groups (an electronwithdrawing and releasing groups) bonded to the benzene ring. For thepurpose of this invention it is expressively noted that benzene itselfis not regarded as a deactivated compound, and that benzoic acid, andbenzoic acid derivatives are expressively not comprised by the term“deactivated benzene derivative”. Hence, in the context of the presentinvention there is the proviso that the starting compound in the presentinvention is not benzene, not benzoic acid, and not a benzoic acidderivative,

The term “liquid medium” may mean a solvent which inert to fluorinationunder the reaction conditions of the direct fluorination, in which thestarting compound and/or fluorinated target compound may be dissolved,and/or the starting compound itself may be a liquid serving itself asliquid medium, and in which the fluorinated target compound may bedissolved if it is not a liquid, or if it is a liquid may also serve asthe liquid medium.

The numerical ranges disclosed herein include all values from, andincluding, the lower and upper value. For ranges containing explicitvalues (e.g., 1 to 7), any subrange between any two explicit values isincluded (e.g., 1 to 2; 2 to 6; 5 to 7; 3 to 7; 5 to 6; etc.).

The terms “comprising,” “including,” “having,” and their derivatives,are not intended to exclude the presence of any additional component,step or procedure, whether or not the same is specifically disclosed. Inorder to avoid any doubt, all compositions claimed through use of theterm “comprising” may include any additional additive, adjuvant, orcompound, whether polymeric or otherwise, unless stated to the contrary.In contrast, the term, “consisting essentially of” excludes from thescope of any succeeding recitation any other component, step, orprocedure, excepting those that are not essential to operability. Theterm “consisting of” excludes any component, step, or procedure notspecifically delineated or listed. The term “or,” unless statedotherwise, refers to the listed members individually as well as in anycombination. Use of the singular includes use of the plural and viceversa.

The term “vol.-%” as used herein means “% by volume”. Unless otherwisestated, all percentages (%) as used herein denote “vol.-%” or “% byvolume”, respectively.

For example, the use of the term “essentially”, in referring to afluorination gas consisting essentially of F₂-gas as it directly comesout of the F₂-electrolysis reactors (fluorine cells), means thatproviding such F₂-gas does not involve major purification and/orproviding another gas, e.g., an inert gas, separate and/or in admixturein amounts and/or under conditions that would be sufficient to provide achange in the composition of an F₂-gas as produced in and as it iswithdrawn as gaseous product from F₂-electrolysis reactors (fluorinecells) of more than about ±5% by volume, or preferably of more thanabout ±3% by volume. Accordingly, such a fluorination gas consistingessentially of F₂-gas as it directly comes out of the F₂-electrolysisreactors (fluorine cells) is meant to comprise elemental fluorine (F₂)in a concentration of at least about 92% by volume, or preferably of atleast about 95% by volume. Especially, such a fluorination gasconsisting essentially of F₂-gas as it directly comes out of theF₂-electrolysis reactors (fluorine cells) may comprise elementalfluorine (F₂) in a concentration in a range of about 92-100% by volume,or preferably in a range of about 95-100% by volume, or more preferablyin a range of in a range of about 92-99% by volume, or preferably in arange of about 95-99% by volume, or in a range of in a range of about 92to about 97% by volume, or preferably in a range of about 95 to about97% by volume.

The numerical ranges disclosed herein include all values from, andincluding, the lower and upper value. For ranges containing explicitvalues (e.g., 1 to 7), any subrange between any two explicit values isincluded (e.g., 1 to 2; 2 to 6; 5 to 7; 3 to 7; 5 to 6; etc.).

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows fluorination using a gas scrubber system.

FIG. 2 shows continuous fluorination in a one or several microreactor(in series) system.

FIG. 3 shows continuous distillation of CF3CN out of synthesis with F2.

FIG. 4 shows continuous distillation of NF3 crude material out ofsynthesis with high conc. F2.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

As briefly described in the Summary of the Invention, and defined in theclaims and further detailed by the following description and examplesherein, the invention is particularly making use of a fluorination gas,wherein the elemental fluorine (F₂) is present in a high concentration,and to a process for the manufacture of a fluorinated inorganic compoundor a fluorinated organic compound, respectively, by direct fluorinationemploying a fluorination gas, wherein the elemental fluorine (F₂) ispresent in a high concentration.

The invention makes use of a fluorination gas, wherein the elementalfluorine (F₂) is present in a high concentration, for example, in aconcentration of elemental fluorine (F₂) especially of equal to muchhigher than 15% or 20% by volume (i.e., at least 15% or 20% by volume),and preferably at least 25% by volume, to a process for the manufactureof a fluorinated inorganic compound or a fluorinated organic compound,respectively, by direct fluorination employing a fluorination gas,wherein the elemental fluorine (F₂) is present in a high concentration.The process of the invention is directed to the manufacture of afluorinated inorganic compound or a fluorinated organic compound,respectively, by direct fluorination, especially is of interest in themanufacture or preparation of a fluorinated inorganic compound or afluorinated organic compound, respectively, as final products and aswell intermediates, for usage in agro-, pharma-, electronics-, catalyst,solvent and other functional chemical applications. The fluorinationprocess of the invention may be performed batch-wise or in a continuousmanner. If the process of the invention is performed batch-wise, acolumn (tower) reactor may be used. If the process of the invention iscontinuous a microreactor may be used. If desired, it is also possibleto perform the process of the invention continuously in a column (tower)reactor (gas scrubber system). However, it is preferred to perform acontinuous process of the invention in a microreactor.

Especially, in one aspect the invention is directed to the use of afluorination gas, wherein elemental fluorine (F₂) is present in a highconcentration of substantially more than, in particular very much morethan at least 10% by volume of elemental fluorine (F₂), especially ofequal to much higher than 15% or 20% by volume (i.e., at least 15% or20% by volume), and preferably at least 25% by volume, for themanufacture of a fluorinated inorganic compound or a fluorinated organiccompound, respectively, in a liquid medium comprising or consisting of astarting compound having one or more hydrogen atoms that are capable ofbeing substituted by means of a halogenation reaction, preferablywherein the fluorine (F₂) is present in the fluorine containing gas in ahigh concentration in a range of from substantially more than, inparticular very much more than 15% or 20% by volume (i.e., at least 15%or 20% by volume), and preferably at least 20% by volume, each up to100% by volume, preferably equal to or more than 25% by volume and up to100% by volume (vol.-%).

In this invention it now was found that, preferably in special equipmentand with special reactor design such as, e.g., a microreactor or apacked bed tower (preferably made of Hastelloy), especially a packed bedtower containing fillers, e.g., metal fillers (e.g. Hastelloy) orplastic fillers, preferably wherein the tower (e.g., made out ofHastelloy) is filled either with E-TFE or metal fillings (Hastelloy),for example each of about 10 mm diameter as available from Raschig(http://www.raschig.de/Fllkrper). The type of fillings is quiteflexible, Raschigs Pall-Rings made out of Hastelloy can be used, andadvantageously E-TFE-fillings.

In the said special equipment and with special reactor design such as,e.g., a microreactor or a packed bed tower (preferably made ofHastelloy), a fluorine gas with concentrations of substantially morethan, in particular very much higher than 15% or 20% by volume ofelemental fluorine (F₂), especially of equal to much higher than 20% byvolume (i.e., at least 20% by volume) of elemental fluorine (F₂),preferably of equal to much higher than 25% by volume of elementalfluorine (F₂), can be used for chemical synthesis especially for thepreparation of a fluorinated inorganic compound or a fluorinated organiccompound, respectively, as final products and/or intermediates, forusage in agro-, pharma-, electronics-, catalyst, solvent and otherfunctional chemical applications. This invention allows fluorinationchemistry with F₂ gas with concentrations preferably equal tosubstantially more than, in particular very much higher than 25% byvolume of elemental fluorine (F₂). In a applying the presentfluorination process it is possible to perform chemistry with F₂ as itcomes directly out of the F₂-electrolysis reactors (fluorine cells). Arepresentative composition of fluorine gas produced by a fluorine cellis 97% F₂, up to 3% CF₄ (formed from damage of the electrodes), forexample, traces of HF, NO₂, OF₂, COF₂, each % by volume and based on thetotal volume of the fluorine containing gas as 100% by volume. Regardingthe scope of the present invention it is to be noted that, that forlegal reason only but not for technical reason, there is a proviso thatthe starting compound, to be reacted with the fluorination gas, is notbenzene, not benzoic acid, and not a benzoic acid derivative, and thefluorinated compound produced is not a fluorinated benzene, and inparticular the fluorinated compound produced is not fluorobenzene ormonofluorbenzene.

In the fluorination gas the elemental fluorine (F₂) may be diluted by aninert gas. The inert gas then constitutes the substantial difference(e.g., there may be only minor quantities of by-products (e.g., CF₄) ofno more than about 5% by volume, preferably of no more than about 3% byvolume, and only traces impurities (e.g., such like HF, NO₂, OF₂, COF₂),in the fluorination gas).

An inert gas is a gas that does not undergo chemical reactions under aset of given conditions.

The noble gases often do not react with many substances and werehistorically referred to as the inert gases. Inert gases are usedgenerally to avoid unwanted chemical reactions degrading a sample. Theseundesirable chemical reactions are often oxidation and hydrolysisreactions with the oxygen and moisture in air.

Typical inert gases are noble gases, and the very common inert gasnitrogen (N₂). The noble gases (historically also the inert gases;sometimes referred to as aerogens) make up a group of chemical elementswith similar properties; under standard conditions, they are allodorless, colorless, monatomic gases with very low chemical reactivity.The six noble gases that occur naturally are helium (He), neon (Ne),argon (Ar), krypton (Kr), xenon (Xe), and the radioactive radon (Rn).

Purified argon and nitrogen gases are most commonly used as inert gasesdue to their high natural abundance (78.3% N2, 1% Ar in air) and lowrelative cost. The preferred is nitrogen (N₂) as the inert gas fordiluting the elemental fluorine (F₂) in the fluorination gas to thedesired but still high concentration, as defined herein.

Preferred is a fluorination gas, wherein the elemental fluorine (F₂) isdiluted by nitrogen (N₂). An example composition of a fluorination gas,using nitrogen (N₂) as the inert gas, is as follows (here as purifiedcomposition (fluorine-nitrogen gas mixture) as filled in a steel gascylinder):

Molecular Formula: F₂ Molecular Weight: 38 Item Index F₂ content (volumefraction)/10⁻² 20 N₂ content (volume fraction)/10⁻² 80 O₂ content(volume fraction)/10⁻² ≤0.08 CF₄ content (volume fraction)/10⁻² ≤0.03 HFcontent (volume fraction)/10⁻² ≤0.50 Properties: melting point: −218°C., boiling point: −187° C., relative densitiy (moisture = 1) 1.14(−200° C.), soluble in water, relative density (air = 1) 1.70, saturatedvapor pressure (kpa): 101.32 (−187° C.), critical pressure (MPA): 5.57.

The following two FIGS. 1 and 2 illustrate the industrial options to useF₂ gas with little or even with no dilution with inert gas:

FIG. 1: Fluorination using a gas scrubber system.

Batch fluorination with highly concentrated F₂ gas in a counter-currentsystem (the reservoir is containing the liquid raw material oroptionally the raw material in an inert solvent). If highly concentratedF₂ is used together with some inert gas (e.g. 10% N₂) the pressureduring the fluorination is kept at 20 bar by a pressure valve. The inertgas together with (only) some HF leaves as purge gas during reaction.

FIG. 2: Continuous fluorination in a one or several microreactor (inseries) system.

The raw material reservoir still contains the equimolar formed HF. Thiscan be subjected a batch or continuous distillation or if a solvent ispresent, after removal of the solvent and HF a re-crystallization forpurification. Spray drying is another option depending on the productproperties. A second or even more microreactor in series is just for thepurpose of extending the residence time if needed.

For example, the following compounds or intermediates can be used asstarting compound (inorganic or organic, respectively) or be preparedaccording to this invention (by way of example only, i.e.,non-exhaustive) as indicated in the following schemes:

The fluorination product trifluoroacetonitrile (CF₃CN) can be used asraw material to prepare a conducting salt for lithium ion batteries.

However, regarding the scope of the present invention it is to be notedthat, that for legal reason only but not for technical reason, there isa proviso that the use of trifluoroacetonitrile (CF₃CN) in themanufacture of a conducting salt for lithium ion batteries, any processfor the manufacture of a conducting salt for lithium ion batteriesderived from trifluoroacetonitrile (CF₃CN), and the conducting salt forlithium ion batteries itself derived from such use or manufactureincluding in at least one step trifluoroacetonitrile (CF₃CN), isexcluded from the scope of the present invention. The scope of thepresent invention, therefore, is limited to the manufacture oftrifluoroacetonitrile (CF₃CN) by direct fluorination with a fluorinationgas comprising or consisting of a highly concentrated F₂-gas.

The fluorination product trifluorosulfonylfluoride (CF₃SO₂F) can be usedas raw material to prepare a conducting salt for lithium ion batteries.

However, regarding the scope of the present invention it is to be notedthat, that for legal reason only but not for technical reason, there isa proviso that the use of trifluorosulfonylfluoride (CF₃SO₂F) in themanufacture of a conducting salt for lithium ion batteries, any processfor the manufacture of a conducting salt for lithium ion batteriesderived from trifluorosulfonylfluoride (CF₃SO₂F), and the conductingsalt for lithium ion batteries itself derived from such use ormanufacture including in at least one step trifluorosulfonylfluoride(CF₃SO₂F), is excluded from the scope of the present invention. Thescope of the present invention, therefore, is limited to the manufactureof trifluorosulfonylfluoride (CF₃SO₂F) by direct fluorination with afluorination gas comprising or consisting of a highly concentratedF₂-gas.

CF₃OF (trifluoromethylhypofluorite) is a fluorinating reagent for theproduction of polyfluoroether as “functional fluids”, e.g. EP0267627 A1(Ausimont). CF₃OF (trifluoromethylhypofluorite) is also useful for theproduction of SF₄ (also already described by Roger et al. in Journal ofthe American Chemical Society Volume 79, 1957, 5625-5627) a fluorinatingagent to convert OH-groups to F or Carbonyl groups to CF₂ under mildconditions. Another industrially very important usage of CF₃OF accordingto present invention is the application in production of highest purityLiF (out of Li₂CO₃) which is used for Li-battery conducting salt andother applications in electronics (see Roger et al. JACS reference citedhere above): CF₃OF+2 Li₂CO₃=>3 CO₂+4 LiF+0.5 O₂.

Monofluoro acetic acid is a monofluorine building block and the sodiummonofluoro acetate is an active ingredient for agro-chemicals. Ofcourse, monofluoro acetic acid can also be prepared from the monofluoroacetonitrile.

The fluoroacrylate is the raw material for the Patiromer® (preparationfor renal patients) of Relypsa, see U.S. Pat. No. 9,061,990. Thisreaction has been described in the microreactor (EP2664607), but onlywith diluted fluorine.

Fluoromalonic ester production with F₂ is known, but only with dilutedfluorine. Fluoromalonic ester is a key building block for an activeingredient for agro-chemicals.

Fluorination of many 1,3-dicarbonyl methylene compounds; in principleall reactions listed in WO 95/14646 are possible, too, to be performedby the present invention like fluorinated acetyl acetone, fluorinatedacetoacetates as well as fluorinated cyclic cyclopentanoneandcyclohexanone derivatives, especially for example, to provide followingproducts:

In 2-position fluorinated acetacetates and cyclohexanone acetates andCyclopentanone acetates can be used as starting material for producingmonofluoroacetones, difluoroacetones, and monofluorocyclohexanone andmonofluorocyclopentanone after transesterification/decarboxylationprepared according to the principle disclosed in EP623577.

If hexafluoroacetylacetone or trifluoroacetylacetone is used as startingmaterial the perfluorinatedoctofluoroacetylacetone might haveapplication in electronics industries like additives for batteries; thisexample is not given in previously mentioned WO 95/14646.

Important compounds are also:

product

The mentioned perfluorinatedoctafluoroacetylacetone can alternatively beprepared by fluorinating acetylacetone with 8 equivalents of F₂according to this invention.

These (also multiply) fluorinated ethylene carbonates can all be madefrom ethylene carbonate (EC), but with altered F₂ stoichiometry.

5-membered heterocycles are described in Gazzettachimicaitaliana 120(12) (1990), pp. 749. There deep temperatures and low(er) selectivitiesare mentioned. In contrary to this work, the process of this inventionin a microreactor delivers with 95% selectivity the 2-Fluorothiopheneand only traces of the 3-fluoro thiophene, the fluorination allowshigher temperatures at 5−10° C. for the reaction compared to −63° C. inknown procedure. Similar result can be obtained with N-methylpyrrolegiving mainly the 3-fluoro-N-methylpyrrole.

Also, in contrary to the known chemistry giving 1,4-difluorinatedproduct, conversion of furane with F₂ at 5° C. in a microreactor in theframework of this invention gives 2-fluorofurane with 81% yield.

The 1-methyl-5-fluorouracil(5-fluoro-1-methyl-2,4(1H,3H)-pyrimidinedione) as 5-fluorouracilderivative can be prepared out of 1-methyluracil and the5-fluoro-3-methylcytosine as a cytosine derivative can be prepareddirectly out of 3-methylcytosine by direct fluorination according tothis invention instead of a more complicated methylation reaction out ofthe 5-fluorouracil as described by Kuz′menko, I. I.; et alZhurnalObshcheiKhimii (1989), 59(8), 1751-5 for the fluoromethyluraciland described in WO 2013/025795 for the preparation of5-fluoro-3-methylcytosine even applying a kind of sophisticatedprotecting group chemistry, this also avoids usage of CF₃OF which wouldrequire two more chemical steps.

A particular compound that may be obtained by the process of the presentinvention is the compound fluorocyanide (F—CN), preferably fluorocyanide(F—CN) obtainable or obtained by a process according to any of theprocess embodiments of the invention, in situ or in isolated form.

The said compound of fluorocyanide (F—CN), i.e., as produced accordingto the process of this invention, is novel and is provided for the firsttime by the present invention in excellent purity. Accordingly, in thisaspect the invention is also directed to the compound of fluorocyanide(F—CN), preferably fluorocyanide (F—CN) obtainable or obtained by aprocess according to any of the process embodiments of the invention, insitu or in isolated form.

The fluorination product fluorocyanide (F—CN) can be used as rawmaterial to prepare a conducting salt for lithium ion batteries.

However, regarding the scope of the present invention it is to be notedthat, that for legal reason only but not for technical reason, there isa proviso that the use of fluorocyanide (F—CN) in the manufacture of aconducting salt for lithium ion batteries, any process for themanufacture of a conducting salt for lithium ion batteries derived fromfluorocyanide (F—CN), and the conducting salt for lithium ion batteriesitself derived from such use or manufacture including in at least onestep fluorocyanide (F—CN), is excluded from the scope of the presentinvention. The scope of the present invention, therefore, is limited tothe manufacture of fluorocyanide (F—CN) by direct fluorination with afluorination gas comprising or consisting of a highly concentratedF₂-gas.

Fluorination of Deactivated Benzene Derivatives:

According to the present invention it is also possible to fluorinatedeactivated benzene derivatives by the direct fluorination process asdefined herein using, in contrast to Chambers et al. (see supra), afluorination gas comprising or consisting of highly concentratedelemental fluorine (F₂). Examples for such direct fluorinations,according to the invention, of deactivated benzene derivatives are givenhereunder in Schemes 13 and 14. The definition of “deactivated benzenederivatives” is given further above. It is to be noted that benzeneitself is not regarded as a “deactivated” compound.

These direct fluorination reactions may be performed in a solvent whichis inert to fluorination under the reaction conditions, for example, thesolvent may be acetonitrile (CH₃CN). It is noted that the benzene ringof the deactivated benzene derivatives has a higher reactivity than thesolvent, e.g., acetonitrile, regarding the direct fluorination reaction.

In such a case, wherein the fluorination is carried out in a solvent,then the direct fluorination according to the invention isadvantageously performed using slightly sub-molar amounts of thefluorination gas comprising highly concentrated F₂-gas. This isparticularly the case when deactivated benzene derivatives are used asthe starting compound, as further described below, for the startingcompounds in Schemes 13 and 14 are solids, and therefore, a solvent(acetonitrile) is used.

Further, it has been discovered that despite the exothermic character ofthe direct fluorination reaction, e.g., within a given time period(e.g., less than 10 hours, or even less than 5 hours), the reaction ofthe invention can be performed as a larger scale reaction with highconversion rates, and without major impurities in the resultingfluorinated product. The fluorinated product can be produced in kilogramscale quantities, e.g., the direct fluorination process of the inventioncan be performed in a large-scale and/or industrial production of afluorinated deactivated benzene compound. For reason of calculatingquantities, as an example but not intended to be limiting, reference ismade to the molecular weight of 1,3-dinitro-benzene of 168.11 g/mol, andof fluoro-1,3-dinitro-benzene of 186.10 g/mol (see Example 13); and to3-nitro-benzonitrile of 148.12 g/mol, and of3-fluoro-5-nitro-benzonitrile of 168.11 g/mol (see Example 14).

Accordingly, it is preferred that the direct fluorination process of theinvention is performed in a large-scale and/or industrial production ofa fluorinated deactivated benzene compound, e.g., in kilogram scalequantities, wherein at least about 0.1 kg/h of deactivated benzenecompound as the starting material is fluorinated per hour, preferably atleast about 0.3 kg/h of deactivated benzene as the starting material isfluorinated per hour, to yield a fluorinated deactivated benzenecompound, with a conversion of at least 70%, preferably about at least75% or even at least 85% conversion; and/or with a product yield of atleast 70%, preferably about at least 75% or even at least 85%.

Accordingly, it is preferred that the direct fluorination process of theinvention is performed in a large-scale and/or industrial production ofa fluorinated deactivated benzene compound, e.g., in a larger scale oreven kilogram scale quantities, e.g., within a given time period,wherein in a microreactor process, in a continuous process, as describedherein, at least about 0.5 mol/h deactivated benzene compound, or atleast about 1 mol/h, preferably at least about 2 mol/h, more preferablyat least about 2.5 mol/h or 3 mol/h, of a deactivated benzene compoundas the starting material is fluorinated for a desired period of time(e.g., of at least 0.5 h, preferably of at least 1 h, more preferably ofat least 2, 3, or 4 h) to produce the required large-scale and/orindustrial scale quantity of fluorinated deactivated benzene compound,with a conversion of at least 70%, preferably about at least 75% or evenat least 85% conversion; and/or with a product yield of at least 70%,preferably about at least 75% or even at least 85%.

The reaction is performed with an equimolar amount of highlyconcentrated F₂-gas, and optionally in a slight molar excess amount ofabout 0.01 to about 0.1 mol/h, but preferably in a slight sub-molaramount of about −0.01 to about 0.1 mol/h, more preferably in a slightsub-molar amount of about −0.02 to about −0.09 mol/h, even morepreferably of about −0.03 to about −0.08 mol/h, most preferably of about−0.5 to about −0.07 mol/h, of highly concentrated F₂-gas.

A fluoro-dinitro-benzene is described for the use in cancer therapy(U.S. Pat. No. 5,290,551), in CN 1360888 the use for skin diseases isclaimed.

The 3-fluoro-5-nitro-benzonitrile is claimed when used against AIDs(see, e.g., WO 2018/002848).

Fluorination with Fluorination Gas Containing Elemental Fluorine in aHigh Concentration:

As briefly described, and defined in the claims and further detailed bythe following description and examples herein, the invention isparticularly directed to a use of a fluorination gas, wherein theelemental fluorine (F₂) is present in a high concentration, and to aprocess for the manufacture of a fluorinated inorganic compound orfluorinated organic compound, respectively, by direct fluorinationemploying a fluorination gas, wherein the elemental fluorine (F₂) ispresent in a high concentration. This particular aspect of the inventionshall be further explained herein after.

As shown in the examples, the direct fluorination can be performedalready with a fluorination gas, based on the total fluorination gascomposition as 100% by volume, comprising at least 20% by volume ofelemental fluorine (F₂) and up to about 80% by volume of an inert gas,preferably nitrogen (N₂), for example, the composition of a fluorinationgas, using nitrogen (N₂) as the inert gas, as described above aspurified composition fluorine-nitrogen gas mixture as filled in a steelgas cylinder.

By the present invention it was found that the fluorination processaccording to the invention is already feasible with a fluorination gas,based on the total fluorination gas composition as 100% by volume,comprising at least 20% by volume of elemental fluorine (F₂), but for anindustrial process undesirably low conversion rates of only about up to30 to 45% are achieved.

Surprisingly it was also found that the use of inert gas in largerratios of inert gas to elemental fluorine has disadvantages in terms ofprocess controllability of the fluorination reaction, for example, interms of effective mixing of the elemental fluorine with the liquidcompound to be fluorinated, heat transfer control, e.g., poor heatexchange, and maintenance of desired reaction conditions in themicro-environments in the reaction mixture. These disadvantages equallyapply in bed tower reactor (gas scrubber system) technology and inmicrobubble microreactor or comparable continuous flow technology. Forexample, in a coil reactor or microreactor, at high inert gasconcentrations, e.g., low fluorine (F₂) concentrations, in addition tothe poor heat exchange, there are also ineffective (reaction) zones with(inert) gas bubbles, which nullifies the advantages of using a coilreactor or a microreactor, and the same is observed in bed tower reactor(gas scrubber system) technology.

However, it was also found by the present invention that, based on thetotal fluorination gas composition as 100% by volume, increasing theconcentration of elemental fluorine (F₂) in the fluorination gas to ahigher concentration of greater than 20% by volume, e.g., preferably ofgreater than 25% by volume, more preferably of greater than 30% byvolume or 40% by volume, and most preferably of greater than 50% byvolume, while on the other hand decreasing the concentration of theinert gas, e.g., of the inert gas nitrogen (N₂), to a correspondinglower concentration of less than 80% by volume, e.g., preferably of lessthan 75% by volume, more preferably of less than 70% by volume or 60% byvolume, and most preferably of less than 50% by volume, for anindustrial process gradually increasing conversion rates of essentiallyabove about 30 to 45%, e.g. conversion rates of more than 50% by volume,preferably of more than 60% by volume, or more than 70% by volume, ormore than 70% by volume, even more preferably of more than 80% byvolume, and most preferably of more than 90% by volume, can be achieved.

Without wishing to be bound to a theory, it is estimated that the inertgas used to dilute the reactivity of the strongly oxidant elementalfluorine (F₂), which is required for safety reasons when handling andtransporting elemental fluorine (F₂) as described in the backgroundabove (e.g., in Europe mixtures of 95% by volume N2 (inert gas) withonly 5% by volume F₂-gas, or in Asia, e.g., at least 80% by volume N2(inert gas) with only up to 20% by volume F₂-gas) is jeopardizing thefluorination reaction, despite the fact that the elemental fluorine (F₂)contained in such a diluted fluorination gas still is strong oxidant.

Surprisingly, by the present invention it was found, that directfluorination of compounds with even higher conversion rates than thoseobtained with the said conventional diluted fluorination gases can beachieved, if the elemental fluorine (F₂) is undiluted by inert gas, orelemental fluorine (F₂) is diluted by inert gas only to a concentrationof greater than 50% by volume elemental fluorine (F₂) in thefluorination gas, based on the total fluorination gas composition as100% by volume.

Therefore, it is particularly preferred by the present invention toprovide a fluorination process for the manufacture or preparation of afluorinated inorganic compound or a fluorinated organic compound,respectively, by direct fluorination using fluorine gas (F₂), as itcomes directly out of a F₂-electrolysis reactor (fluorine cell).

A representative composition of fluorine gas produced by a fluorine cellis 97% F₂, up to 3% CF₄ (formed from damage of the electrodes), tracesof HF, NO₂, OF₂, COF₂, each % by volume and based on the total volume ofthe fluorine containing gas as 100% by volume.

Purification of the fluorination gas as it is derived from aF₂-electrolysis reactor (fluorine cell), if desired, optionally ispossible, to remove a part or all by-products and traces formed in theF₂-electrolysis reactor (fluorine cell), prior to its use asfluorination gas in the process of the present invention. However, inthe process of the present invention such a partial or completepurification is not required, and the fluorination gas can be directlyused, as it comes directly out of a F₂-electrolysis reactor (fluorinecell).

When employing a fluorination gas derived from a F₂-electrolysis reactor(fluorine cell), purified or unpurified, it may, if desired, optionallybe diluted to some extent by an inert gas, preferably by nitrogen (N₂).

Hence, such a fluorination gas, purified or unpurified, as it is derivedfrom a F₂-electrolysis reactor (fluorine cell), if desired, mayoptionally be diluted by up to about 45% by volume of inert gas, butpreferably the fluorination gas is not diluted by inert gas to aconcentration of elemental fluorine (F₂) in the fluorination gas of less80% by volume, preferably of less than 85% by volume, more preferably ofless than 90% by volume, based on the total fluorination gas compositionas 100% by volume.

The difference of the sum of the elemental fluorine (F₂) and any inertgas in the fluorination gas to 100% by volume, if any difference, may beconstituted by by-products (e.g., CF₄) and traces of HF, NO₂, OF₂, COF₂,formed from damage of the electrodes of the F₂-electrolysis reactor(fluorine cell). This applies generally to the % by volume values givenherein above and herein below, if fluorine gas (F₂), as it comesdirectly out of a F₂-electrolysis reactor (fluorine cell) is used as thefluorination gas in the present invention.

Accordingly, in a preferred process of the invention the directfluorination is carried out with a fluorination gas comprising about 80%by volume to 97±1% of elemental fluorine (F₂) and about 0% to 17±1% ofinert gas, preferably of nitrogen (N₂), based on the total fluorinationgas composition as 100% by volume.

In a further preferred process of the invention the direct fluorinationis carried out with a fluorination gas comprising about 85% by volume to97±1% of elemental fluorine (F₂) and about 0% to 12±1% of inert gas,preferably of nitrogen (N₂), based on the total fluorination gascomposition as 100% by volume.

In a furthermore preferred process of the invention the directfluorination is carried out with a fluorination gas comprising about 87%by volume to 97±1% of elemental fluorine (F₂) and about 0% to 10±1% ofinert gas, preferably of nitrogen (N₂), based on the total fluorinationgas composition as 100% by volume.

In another preferred process of the invention the direct fluorination iscarried out with a fluorination gas comprising about 90% by volume to97±1% of elemental fluorine (F₂) and about 0% to 7±1% of inert gas,preferably of nitrogen (N₂), based on the total fluorination gascomposition as 100% by volume.

In still another preferred process of the invention the directfluorination is carried out with a fluorination gas comprising about 95%by volume to 97±1% of elemental fluorine (F₂) and about 0% to 2±1% ofinert gas, preferably of nitrogen (N₂), based on the total fluorinationgas composition as 100% by volume.

It goes without saying that a person skilled in the art understands thatwithin any of the given ranges any intermediate values and intermediateranges can be selected, too.

Use of Fluorination Gas with High Concentration of Elemental Fluorine:

The invention also relates to a use of a fluorination gas, whereinelemental fluorine (F₂) is present in a high concentration ofsubstantially more than, in particular very much more than 15% by volumeor in particular than 20% by volume of elemental fluorine (F₂),especially of equal to much higher than 25% by volume, i.e., at least25% by volume, of elemental fluorine (F₂), preferably of equal to muchhigher than 35% by volume or in particular than 45% by volume, for themanufacture of a fluorinated inorganic compound or a fluorinated organiccompound, respectively, in a liquid medium comprising or consisting ofan inorganic compound or an organic compound, respectively, each asstarting compound (wherein the one or more hydrogen atoms that arecapable of being substituted by means of a halogenation reaction), withthe proviso that the starting compound is not benzene, not benzoic acid,and not a benzoic acid derivative, and the fluorinated compound producedis not a fluorinated benzene, especially not monofluorobenzene.

In general, in one aspect the invention is also directed to the use of afluorination gas, wherein the elemental fluorine (F₂) is present in ahigh concentration, e.g., a use in a process for the manufacture of afluorinated inorganic compound or a fluorinated organic compound,respectively, in a liquid medium comprising or consisting of a startingcompound having one or more hydrogen atoms that are capable of beingsubstituted by means of a halogenation reaction, according to theinvention, with the proviso that the starting compound is not benzene,not benzoic acid, and not a benzoic acid derivative, and the fluorinatedcompound produced is not a fluorinated benzene, especially notmonofluorobenzene, wherein the elemental fluorine (F₂) is present in thefluorination gas in a high concentration of at least 25% by volume,preferably of at least 30% by volume, more preferably of at least 35% byvolume, even more preferably of at least 45% by volume, each based onthe total volume of the fluorination gas as 100% by volume.

Furthermore, in the said use, the elemental fluorine (F₂) can be presentin the fluorination gas in a high concentration of at least 45% byvolume, preferably of at least 50% by volume, more preferably of atleast 60% by volume, even more preferably of at least 70% by volume, orof at least 80% by volume, each based on the total volume of thefluorination gas as 100% by volume.

In the said use for the manufacture of a fluorinated compound accordingto the invention, in an embodiment the elemental fluorine (F₂) ispresent in the fluorination gas in a high concentration of at least 15%by volume, preferably of at least 20% by volume, or of at least 25% byvolume, more preferably of at least 30% by volume, even more preferablyof at least 40% by volume, each based on the total volume of thefluorination gas as 100% by volume.

Furthermore, in the said use, the elemental fluorine (F₂) can be presentin the fluorination gas in a high concentration of at least 45% byvolume, preferably of at least 50% by volume, more preferably of atleast 60% by volume, even more preferably of at least 70% by volume, orof at least 80% by volume, each based on the total volume of thefluorination gas as 100% by volume.

In the said use for the manufacture of a fluorinated compound accordingto the invention, in an embodiment the elemental fluorine (F₂) ispresent in the fluorination gas in a high concentration within a rangeof from 15-100% by volume, preferably within a range of from 20-100% byvolume, more preferably within a range of from 25-100% by volume, stillmore preferably within a range of from 30-100% by volume, even morepreferably within a range of from 35-100% by volume, an still morepreferred within a range of from 45-100% by volume, each based on thetotal volume of the fluorination gas as 100% by volume.

Furthermore, in the said use, the elemental fluorine (F₂) can be presentin the fluorination gas in a high concentration within a range of from45-100% by volume, preferably within a range of from 50-100% by volume,more preferably within a range of from 60-100% by volume, still morepreferably within a range of from 70-100% by volume, even morepreferably within a range of from 80-100% by volume, each based on thetotal volume of the fluorination gas as 100% by volume.

The Process of the Invention:

As briefly described in the Summary of the Invention, and defined in theclaims and further detailed by the following description and examplesherein, the invention is particularly directed to a process for themanufacture of a fluorinated compound by direct fluorination, whereinthe process comprises the steps of:

-   -   a) provision of a liquid medium comprising or consisting of a        (inorganic or organic) starting compound having one or more        hydrogen atoms that are capable of being substituted by means of        a halogenation reaction;    -   b) provision of a fluorination gas comprising or consisting of        elemental fluorine (F₂), wherein the fluorine is present in the        fluorination gas in a high concentration of at least        substantially more than, in particular very much more than 15%        by volume (vol.-%), preferably equal to or more than 20% by        volume (vol.-%);    -   c) provision of a reactor or reactor system, resistant to        elemental fluorine (F₂) and hydrogen fluoride (HF);    -   d) passing the fluorination gas of b), in a reactor or reactor        system of c), through the liquid medium of a) comprising or        consisting of the (inorganic or organic) starting compound, and        thereby reacting the (inorganic or organic) starting compound        with the elemental fluorine (F₂) to substitute in the (inorganic        or organic) starting compound at least one of the one or more        hydrogen atoms for fluorine, and wherein the reaction is carried        out at temperature of from about −30° C. to about +100° C. and a        pressure of from about 1 bar absolute bar to about 20 bar        absolute bar;    -   e) withdrawing the fluorinated (inorganic or organic) compound        formed in step d) from the reactor or reactor system of c);    -   f) to obtain a (inorganic or organic) fluorinated compound        wherein at least one of the one or more hydrogen atoms of the        starting compound is replaced by fluorine atom;

with the proviso that the starting compound is not benzene, not benzoicacid, and not a benzoic acid derivative, and the fluorinated compoundproduced is not a fluorinated benzene, especially not fluorobenzene.

In the said process for the manufacture of a fluorinated compoundaccording to the invention, in an embodiment the elemental fluorine (F₂)is present in the fluorination gas of b) in a high concentration of atleast 25% by volume, preferably of at least 30% by volume, morepreferably of at least 35% by volume, even more preferably of at least45% by volume, each based on the total volume of the fluorination gas as100% by volume.

In the said process for the manufacture of a fluorinated compoundaccording to the invention, in an embodiment the fluorine (F₂) ispresent in the fluorination gas of b) in a high concentration within arange of from 15-100% by volume, preferably within a range of from20-100% by volume, more preferably within a range of from 25-100% byvolume, still more preferably within a range of from 30-100% by volume,even more preferably within a range of from 35-100% by volume, an stillmore preferred within a range of from 45-100% by volume, each based onthe total volume of the fluorination gas as 100% by volume.

In a further embodiment, in the process for the manufacture of afluorinated compound according to the invention, the starting compoundis an inorganic starting compound, preferably an inorganic startingcompound selected from the group consisting of ammonia, hydrogencyanide, hydrazine, tetrafluorohydrazine, difluorodiazine, sulphurhexafluoride (SF₆), and iodine pentafluoride (IF₅).

In a still further embodiment, in the process for the manufacture of afluorinated compound according to the invention, the compound is anorganic starting compound, but is not benzene, preferably wherein thestarting compound is an organic starting compound selected from thegroup consisting of acetonitrile, monofluoro acetonitrile, difluoroacetonitrile, methane sulfonic acid fluoride, monofluoromethane sulfonicacid fluoride, difluoromethane sulfonic acid fluoride, methane sulfonicacid fluoride, ethylene carbonate, monofluoroethylene carbonate,difluoroethylene carbonate, trifluoroethylene carbonate, formaldehyde(H2C═O), difluorophosgene (F₂C═O), 2,2,2-trifluoroethyl methyl ether,acetic acid ethyl ether, monofluoroacetic acid ethyl ether,difluoroacetic acid ethyl ether, methyl acrylate, a malonic acid diesterstarting compound, preferably malonic acid dimethyl ester, a1,3-dicarbonyl methylene starting compound, a C6-aromatic compound, butnot benzene, a deactivated benzene derivative, a C10-aromatic compound,a deactivated C10-aromatic compound, a 5-membered heterocyclic compound,a 6-membered heterocylic compound, a 5-membered heteroaromatic compound,a 6-membered heteroaromatic compound, preferably pyridine, uracil, andcytosine.

Batch Process:

The invention also may pertain to a process for the manufacture of afluorinated compound, wherein the process is a batchwise process,preferably wherein the batchwise process is carried out in a columnreactor. Although, in the following reactor setting the process isdescribed as a batch process, as preferred, for example, in case of highproduct concentrations, optionally the process can be performed in thesaid reactor setting also as a continuous process. In case of acontinuous process in the said reactor setting, then, it goes withoutsaying, the additional inlet(s) and outlet(s) are foreseen, for feedingthe starting compound and withdrawing the product compound,respectively.

If the invention pertains to a batchwise process, preferably wherein thebatchwise process is carried out in a column reactor, the process forthe manufacture of a fluorinated compound according, most preferably thereaction is carried out in a (closed) column reactor (system), whereinthe liquid medium of a) comprising or consisting of the startingcompound is circulated in a loop, while the fluorination gas of b)comprising or consisting of elemental fluorine (F2) in a highconcentration is fed into the column reactor of c) and in step d) ispassed through the liquid medium to react with the starting compound;preferably wherein the loop is operated with a circulation velocity offrom 1,500 l/h to 5,000 l/h, more preferably of from 3,500 l/h to 4,500l/h.

If the invention pertains to a batchwise process, the process for themanufacture of a fluorinated compound according to the invention can becarried out such that the liquid medium of a) comprising or consistingof the starting compound is circulated in the column reactor in aturbulent stream or in laminar stream, preferably in a turbulent stream.

In general, the fluorination gas containing the elemental fluorine (F₂)is fed into the loop in accordance with the required stoichiometry forthe targeted fluorinated product and fluorination degree, and adapted tothe reaction rate.

For example, the said process for the manufacture of a fluorinatedcompound according to the invention, may be performed, e.g., batchwise,wherein the column reactor is equipped with at least one of thefollowing: at least one cooler (system), at least one liquid reservoirfor the liquid medium of a) comprising or consisting of a startingcompound, a pump (for pumping/circulating the liquid medium), one ormore (nozzle) jets, preferably placed at the top of the column reactor,for spraying the circulating medium into the column reactor, one or morefeeding inlets for introducing the fluorination gas of b) comprising orconsisting of elemental fluorine (F₂) in a high concentration,optionally one or more sieves, preferably two sieves, preferably the oneor more sieves placed at the bottom of the column reactor, at least onegas outlet equipped with a pressure valve.

Accordingly, the process for the manufacture of a fluorinated compoundaccording to the invention, can be performed in column reactor which isequipped with at least one of the following:

-   -   (i) at least one cooler (system), at least one liquid reservoir,        with inlet and outlet for, and containing the liquid medium        of a) comprising or consisting of an inorganic compound or        organic compound as the starting compound;    -   (ii) a pump for pumping and circulating the liquid medium of a);    -   (iii) one or more (nozzle) jets, preferably wherein the one or        more (nozzle) jets are placed at the top of the column reactor,        for spraying the circulating medium of a) into the column        reactor;    -   (iv) one or more feeding inlets for introducing the fluorination        gas of b) comprising or consisting of elemental fluorine (F₂) in        a high concentration into the column reactor;    -   (v) optionally one or more sieves, preferably two sieves,        preferably the one or more sieves placed at the bottom of the        column reactor;    -   (vi) and at least one gas outlet equipped with a pressure valve,        and at least one outlet for withdrawing the fluorinated        inorganic compound or organic compound in step e).

In one embodiment, the process for the manufacture of a fluorinatedcompound according to the invention, can be performed in a columnreactor is a packed bed tower reactor, preferably a packed bed towerreactor which is packed with fillers resistant to elemental fluorine(F₂) and hydrogen fluoride (HF), e.g. with Raschig fillers and/or metalfillers, more preferably wherein the packed bed tower reactor is a gasscrubber system (tower) which is packed with fillers resistant toelemental fluorine (F₂) and hydrogen fluoride (HF), e.g. Raschig fillersand/or metal fillers.

In a further embodiment, the process for the manufacture of afluorinated compound according to the invention, the reaction is carriedout with a counter-current flow of the circulating liquid medium of a)comprising or consisting of the starting compound and of thefluorination gas of b) fed into the column reactor and whichfluorination gas of b) is comprising or consisting of elemental fluorine(F₂) in a high concentration.

The pressure valve functions to keep the pressure, as required in thereaction, and to release any effluent gas, e.g. inert carrier gascontained in the fluorination gas, if applicable together with anyhydrogen fluoride (HF) released for the reaction.

The said process for the manufacture of a fluorinated compound accordingto the invention, may be performed, e.g., batchwise, such that in thesaid process for the manufacture of a fluorinated compound the columnreactor is a packed bed tower reactor, preferably a packed bed towerreactor which is packed with metal fillers.

The packed tower according to FIG. 1 can have a diameter of 100 or 200mm (depending on the circulating flow rate and scale) made out of highgrade stainless steel (1.4571) and a length of 3 meters for the 100 mmand a length of 6 meters for the 200 mm diameter tower (latter if highercapacities are needed). The tower made out of Hastelloy is filled eitherwith E-TFE or metal fillings each of 10 mm diameter as available fromRaschig (http://www.raschig.de/Fllkrper). The type of fillings is quiteflexible, Raschigs Pall-Rings made out of Hastelloy were used in thetrials disclosed hereunder, also E-TFE-fillings showed same performance,both not causing too much pressure reduction (pressure loss) whilefeeding F₂-gas in counter-current manner.

In the process for the manufacture of a fluorinated compound accordingto any of the embodiments of the invention, the reaction may be carriedout with a counter-current flow of circulating liquid medium of a)comprising or consisting of the starting compound and the fluorinationgas of b) fed into the column reactor and comprising or consisting ofelemental fluorine (F₂) in a high concentration.

Microreactor Process:

The invention also may pertain to a process for the manufacture of afluorinated compound according to any of the preceding claims, whereinthe process is a continuous process, preferably wherein the continuousprocess is carried out in a microreactor. See FIG. 2.

In general, the fluorination gas containing the elemental fluorine (F2)is fed into the microreactor in accordance with the requiredstoichiometry (sometimes with a slight excess) for the targetedfluorinated product and fluorination degree, and adapted to the reactionrate.

The invention may employ more than a single microreactor, i.e., theinvention may employ two, three, four, five or more microreactors, foreither extending the capacity or residence time, for example, to up toten microreactors in parallel or four microreactors in series. If morethan a single microreactor is employed, then the plurality ofmicroreactors can be arranged either sequentially or in parallel, and ifthree or more microreactors are employed, these may be arrangedsequentially, in parallel or both.

The invention is also very advantageous, in one embodiment wherein thedirect fluorination of the invention optionally is performed in acontinuous flow reactor system, or preferably in a microreactor system.

In an preferred embodiment the invention relates to a process for themanufacture of a fluorinated compound according to the invention,wherein the reaction is carried out in at least one step as a continuousprocesses, wherein the continuous process is performed in at least onecontinuous flow reactor with upper lateral dimensions of about ≤5 mm, orof about ≤4 mm, preferably in at least one microreactor;

-   -   more preferably wherein of the said steps at least (b2) the step        of a fluorination reaction is a continuous process in at least        one microreactor under one or more of the following conditions:    -   flow rate: of from about 10 ml/h up to about 4001/h;    -   temperature: of from about 30° C. up to about 150° C.;    -   pressure: of from about 4 bar up to about 50 bar;    -   residence time: of from about 1 second, preferably from about 1        minute, up to about 60 minutes.

In another preferred embodiment the invention relates to such a processof preparing a compound according to the invention, wherein at least oneof the said continuous flow reactors, preferably at least one of themicroreactors, independently is a SiC-continuous flow reactor,preferably independently is a SiC-microreactor.

The Continuous Flow Reactors and Microreactors:

In addition to the above, according to one aspect of the invention, alsoa plant engineering invention is provided, as used in the processinvention and described herein, pertaining to the optional, and in someembodiments of the process invention, the process even preferredimplementation in microreactors.

As to the term “microreactor”: A “microreactor” or “microstructuredreactor” or “microchannel reactor”, in one embodiment of the invention,is a device in which chemical reactions take place in a confinement withtypical lateral dimensions of about ≤1 mm; an example of a typical formof such confinement are microchannels. Generally, in the context of theinvention, the term “microreactor”: A “microreactor” or “microstructuredreactor” or “microchannel reactor”, denotes a device in which chemicalreactions take place in a confinement with typical lateral dimensions ofabout ≤5 mm.

Microreactors are studied in the field of micro process engineering,together with other devices (such as micro heat exchangers) in whichphysical processes occur. The microreactor is usually a continuous flowreactor (contrast with/to a batch reactor). Microreactors offer manyadvantages over conventional scale reactors, including vast improvementsin energy efficiency, reaction speed and yield, safety, reliability,scalability, on-site/on-demand production, and a much finer degree ofprocess control.

Microreactors are used in “flow chemistry” to perform chemicalreactions.

In flow chemistry, wherein often microreactors are used, a chemicalreaction is run in a continuously flowing stream rather than in batchproduction. Batch production is a technique used in manufacturing, inwhich the object in question is created stage by stage over a series ofworkstations, and different batches of products are made. Together withjob production (one-off production) and mass production (flow productionor continuous production) it is one of the three main productionmethods. In contrast, in flow chemistry the chemical reaction is run ina continuously flowing stream, wherein pumps move fluid into a tube, andwhere tubes join one another, the fluids contact one another. If thesefluids are reactive, a reaction takes place. Flow chemistry is awell-established technique for use at a large scale when manufacturinglarge quantities of a given material. However, the term has only beencoined recently for its application on a laboratory scale.

Continuous flow reactors, e.g. such as used as microreactor, aretypically tube like and manufactured from non-reactive materials, suchknown in the prior art and depending on the specific purpose and natureof possibly aggressive agents and/or reactants. Mixing methods includediffusion alone, e.g. if the diameter of the reactor is narrow, e.g. <1mm, such as in microreactors, and static mixers. Continuous flowreactors allow good control over reaction conditions including heattransfer, time and mixing. The residence time of the reagents in thereactor, i.e. the amount of time that the reaction is heated or cooled,is calculated from the volume of the reactor and the flow rate throughit: Residence time=Reactor Volume/Flow Rate. Therefore, to achieve alonger residence time, reagents can be pumped more slowly, just a largervolume reactor can be used and/or even several microreactors can beplaced in series, optionally just having some cylinders in between forincreasing residence time if necessary for completion of reaction steps.In this later case, cyclones after each microreactor help to let formedHCl to escape and to positively influence the reaction performance.Production rates can vary from milliliters per minute to liters perhour.

Some examples of flow reactors are spinning disk reactors (ColinRamshaw); spinning tube reactors; multi-cell flow reactors; oscillatoryflow reactors; microreactors; hex reactors; and aspirator reactors. Inan aspirator reactor a pump propels one reagent, which causes a reactantto be sucked in. Also to be mentioned are plug flow reactors and tubularflow reactors.

In the present invention, in one embodiment it is particularly preferredto employ a microreactor.

In the use and processes according to the invention in a preferredembodiment the invention is using a microreactor. But it is to be notedin a more general embodiment of the invention, apart from the saidpreferred embodiment of the invention that is using a microreactor, anyother, e.g. preferentially pipe-like, continuous flow reactor with upperlateral dimensions of up to about 1 cm, and as defined herein, can beemployed. Thus, such a continuous flow reactor preferably with upperlateral dimensions of up to about ≤5 mm, or of about ≤4 mm, refers to apreferred embodiment of the invention, e.g. preferably to amicroreactor.Continuously operated series of STRs is another option, but lesspreferred than using a microreactor.

In the before said embodiments of the invention, the minimal lateraldimensions of the, e.g. preferentially pipe-like, continuous flowreactor can be about >5 mm; but is usually not exceeding about 1 cm.Thus, the lateral dimensions of the, e.g. preferentially pipe-like,continuous flow reactor can be in the range of from about >5 mm up toabout 1 cm, and can be of any value therein between. For example, thelateral dimensions of the, e.g. preferentially pipe-like, continuousflow reactor can be about 5.1 mm, about 5.5 mm, about 6 mm, about 6.5mm, about 7 mm, about 7.5 mm, about 8 mm, about 8.5 mm, about 9 mm,about 9.5 mm, and about 10 mm, or can be can be of any valueintermediate between the said values.

In the before said embodiments of the invention using a microreactorpreferentially the minimal lateral dimensions of the microreactor can beat least about 0.25 mm, and preferably at least about 0.5 mm; but themaximum lateral dimensions of the microreactor does not exceed about ≤5mm. Thus, the lateral dimensions of the, e.g. preferential microreactorcan be in the range of from about 0.25 mm up to about ≤5 mm, andpreferably from about 0.5 mm up to about ≤5 mm, and can be of any valuetherein between. For example, the lateral dimensions of the preferentialmicroreactor can be about 0.25 mm, about 0.3 mm, about 0.35 mm, about0.4 mm, about 0.45 mm, and about 5 mm, or can be can be of any valueintermediate between the said values.

As stated here before in the embodiments of the invention in itsbroadest meaning is employing, preferentially pipe-like, continuous flowreactor with upper lateral dimensions of up to about 1 cm. Suchcontinuous flow reactor, for example is a plug flow reactor (PFR).

The plug flow reactor (PFR), sometimes called continuous tubularreactor, CTR, or piston flow reactors, is a reactor used to perform anddescribe chemical reactions in continuous, flowing systems ofcylindrical geometry. The PFR reactor model is used to predict thebehaviour of chemical reactors of such design, so that key reactorvariables, such as the dimensions of the reactor, can be estimated.

Fluid going through a PFR may be modelled as flowing through the reactoras a series of infinitely thin coherent “plugs”, each with a uniformcomposition, traveling in the axial direction of the reactor, with eachplug having a different composition from the ones before and after it.The key assumption is that as a plug flows through a PFR, the fluid isperfectly mixed in the radial direction (i.e. in the lateral direction)but not in the axial direction (forwards or backwards).

Accordingly, the terms used herein to define the reactor type used inthe context of the invention such like “continuous flow reactor”, “plugflow reactor”, “tubular reactor”, “continuous flow reactor system”,“plug flow reactor system”, “tubular reactor system”, “continuous flowsystem”, “plug flow system”, “tubular system” are synonymous to eachother and interchangeably by each other.

The reactor or system may be arranged as a multitude of tubes, which maybe, for example, linear, looped, meandering, circled, coiled, orcombinations thereof. If coiled, for example, then the reactor or systemis also called “coiled reactor” or “coiled system”.

In the radial direction, i.e. in the lateral direction, such reactor orsystem may have an inner diameter or an inner cross-section dimension(i.e. radial dimension or lateral dimension, respectively) of up toabout 1 cm. Thus, in an embodiment the lateral dimension of the reactoror system may be in the range of from about 0.25 mm up to about 1 cm,preferably of from about 0.5 mm up to about 1 cm, and more preferably offrom about 1 mm up to about 1 cm.

In further embodiments the lateral dimension of the reactor or systemmay be in the range of from about >5 mm to about 1 cm, or of from about5.1 mm to about 1 cm.

If the lateral dimension at maximum of up to about ≤5 mm, or of up toabout ≤4 mm, then the reactor is called “microreactor”. Thus, in stillfurther microreactor embodiments the lateral dimension of the reactor orsystem may be in the range of from about 0.25 mm up to about ≤5 mm,preferably of from about 0.5 mm up to about ≤5 mm, and more preferablyof from about 1 mm up to about ≤5 mm; or the lateral dimension of thereactor or system may be in the range of from about 0.25 mm up to about≤4 mm, preferably of from about 0.5 mm up to about ≤4 mm, and morepreferably of from about 1 mm up to about ≤4 mm.

In case reactants are solid inert solvents may be used. Thus, if rawmaterials shall be used, then the said solid raw materials are dissolvedin an inert solvent. A suitable solvent is e.g. acetonitrile, or fullyor partially fluorinated alkanes like Pentafluorobutane (365mfc), linearor cyclic partially or fully fluorinated ethers like CF₃—CH₂—OCHF₂(E245) or Octafluorotetrahydrofuran. Often, if available or after afirst synthesis, the product as such can also serve as inert solvent.

In an alternative embodiment of the invention, it is also optionallydesired to employ another continuous flow reactor than a microreactor,preferably if, for example, the (halogenation promoting, e.g. thehalogenation or preferably the halogenation) catalyst composition usedin the halogenation or fluorination tends to get viscous during reactionor is viscous already as a said catalyst as such. In such case, acontinuous flow reactor, i.e. a device in which chemical reactions takeplace in a confinement with lower lateral dimensions of greater thanthat indicated above for a microreactor, i.e. of greater than about 1mm, but wherein the upper lateral dimensions are about ≤4 mm.Accordingly, in this alternative embodiment of the invention, employinga continuous flow reactor, the term “continuous flow reactor” preferablydenotes a device in which chemical reactions take place in a confinementwith typical lateral dimensions of from about ≥1 mm up to about ≤4 mm.In such an embodiment of the invention it is particularly preferred toemploy as a continuous flow reactor a plug flow reactor and/or a tubularflow reactor, with the said lateral dimensions. Also, in such anembodiment of the invention, as compared to the embodiment employing amicroreactor, it is particularly preferred to employ higher flow ratesin the continuous flow reactor, preferably in the plug flow reactorand/or a tubular flow reactor, with the said lateral dimensions. Forexample, such higher flow rates, are up to about 2 times higher, up toabout 3 times higher, up to about 4 times higher, up to about 5 timeshigher, up to about 6 times higher, up to about 7 times higher, or anyintermediate flow rate of from about ≥1 up to about ≤7 times higher, offrom about ≥1 up to about ≤6 times higher, of from about ≥1 up to about≤5 times higher, of from about ≥1 up to about ≤4 times higher, of fromabout ≥1 up to about ≤3 times higher, or of from about ≥1 up to about ≤2times higher, each as compared to the typical flow rates indicatedherein for a microreactor. Preferably, the said continuous flow reactor,more preferably the plug flow reactor and/or a tubular flow reactor,employed in this embodiment of the invention is configured with theconstruction materials as defined herein for the microreactors. Forexample, such construction materials are silicon carbide (SiC) and/orare alloys such as a highly corrosion resistantnickel-chromium-molybdenum-tungsten alloy, e.g. Hastelloy®, as describedherein for the microreactors.

A very particular advantage of the present invention employing amicroreactor, or a continuous flow reactor with the before said lateraldimensions, the number of separating steps can be reduced andsimplified, and may be devoid of time and energy consuming, e.g.intermediate, distillation steps. Especially, it is a particularadvantage of the present invention employing a microreactor, or acontinuous flow reactor with the before said lateral dimensions, thatfor separating simply phase separation methods can be employed, and thenon-consumed reaction components may be recycled into the process, orotherwise be used as a product itself, as applicable or desired.

In addition to the preferred embodiments of the present invention usinga microreactor according to the invention, in addition or alternativelyto using a microreactor, it is also possible to employ a plug flowreactor or a tubular flow reactor, respectively.

Plug flow reactor or tubular flow reactor, respectively, and theiroperation conditions, are well known to those skilled in the field.

Although the use of a continuous flow reactor with upper lateraldimensions of about ≤5 mm, or of about ≤4 mm, respectively, and inparticular of a microreactor, is particularly preferred in the presentinvention, depending on the circumstances, it could be imagined thatsomebody dispenses with an microreactor, then of course with yieldlosses and higher residence time, higher temperature, and instead takesa plug flow reactor or turbulent flow reactor, respectively. However,this could have a potential advantage, taking note of the mentionedpossibly disadvantageous yield losses, namely the advantage that theprobability of possible blockages (tar particle formation by non-idealdriving style) could be reduced because the diameters of the tubes orchannels of a plug flow reactor are greater than those of amicroreactor.

The possibly allegeable disadvantage of this variant using a plug flowreactor or a tubular flow reactor, however, may also be seen only assubjective point of view, but on the other hand under certain processconstraints in a region or at a production facility may still beappropriate, and loss of yields be considered of less importance or evenbeing acceptable in view of other advantages or avoidance ofconstraints.

In the following, the invention is more particularly described in thecontext of using a microreactor. Preferentially, a microreactor usedaccording to the invention is a ceramic continuous flow reactor, morepreferably a SiC (silicon carbide) continuous flow reactor, and can beused for material production at a multi-to scale. Within integrated heatexchangers and SiC materials of construction, it gives optimal controlof challenging flow chemistry application. The compact, modularconstruction of the flow production reactor enables, advantageously for:long term flexibility towards different process types; access to a rangeof production volumes (5 to 4001/h); intensified chemical productionwhere space is limited; unrivalled chemical compatibility and thermalcontrol.

Ceramic (SiC) microreactors, are e.g. advantageously diffusion bonded 3MSiC reactors, especially braze and metal free, provide for excellentheat and mass transfer, superior chemical compatibility, of FDAcertified materials of construction, or of other drug regulatoryauthority (e.g. EMA) certified materials of construction. Siliconcarbide (SiC), also known as carborundum, is a containing silicon andcarbon, and is well known to those skilled in the art. For example,synthetic SiC powder is been mass-produced and processed for manytechnical applications.

For example, in the embodiments of the invention the objects areachieved by a method in which at least one reaction step takes place ina microreactor. Particularly, in preferred embodiments of the inventionthe objects are achieved by a method in which at least one reaction steptakes place in a microreactor that is comprising or is made of SiC(“SiC-microreactor”), or in a microreactor that is comprising or is madeof an alloy, e.g. such as Hastelloy C, as it is each defined hereinafter in more detail.

Thus, without being limited to, for example, in an embodiment of theinvention the microreactor suitable for, preferably for industrial,production an “SiC-microreactor” that is comprising or is made of SiC(silicon carbide; e.g. SiC as offered by Dow Corning as Type G1 SiC orby Chemtrix MR555 Plantrix), e.g. providing a production capacity offrom about 5 up to about 400 kg per hour; or without being limited to,for example, in another embodiment of the invention the microreactorsuitable for industrial production is comprising or is made of HastelloyC, as offered by Ehrfeld. Such microreactors are particularly suitablefor the, preferably industrial, production of fluorinated productsaccording to the invention.

In order to meet both the mechanical and chemical demands placed onproduction scale flow reactors, Plantrix modules are fabricated from3M™SiC (Grade C). Produced using the patented 3M (EP 1 637 271 B1 andforeign patents) diffusion bonding technology, the resulting monolithicreactors are hermetically sealed and are free from welding lines/jointsand brazing agents. More technical information on the Chemtrix MR555Plantrix can be found in the brochure “CHEMTRIX—Scalable FlowChemistry—Technical Information Plantrix® MR555 Series, published byChemtrix BV in 2017, which technical information is incorporated hereinby reference in its entirety.

Apart from the before said example, in other embodiments of theinvention, in general SiC from other manufactures, and as known to theskilled person, of course can be employed in the present invention.

Accordingly, in the present invention as microreactor also the Protrix®of by Chemtrix can be used. Protrix® is a modular, continuous flowreactor fabricated from 3M® silicon carbide, offering superior chemicalresistance and heat transfer. In order to meet both the mechanical andchemical demands placed on flow reactors, Protrix® modules arefabricated from 3M® SiC (Grade C). Produced using the patented 3M (EP 1637 271 B1 and foreign patents) diffusion bonding technology, theresulting monolithic reactors are hermetically sealed and are free fromwelding lines/joints and brazing agents. This fabrication technique is aproduction method that gives solid SiC reactors (thermal expansioncoefficient=4.1×10-6K⁻¹).

Designed for flow rates ranging from 0.2 to 20 ml/min and pressures upto 25 bar, Protrix® allows the user to develop continuous flow processesat the lab-scale, later transitioning to Plantrix® MR555 (×340 scalefactor) for material production. The Protrix® reactor is a unique flowreactor with the following advantages: diffusion bonded 3M® SiC moduleswith integrated heat exchangers that offer unrivaled thermal control andsuperior chemical resistance; safe employment of extreme reactionconditions on a g scale in a standard fumehood; efficient, flexibleproduction in terms of number of reagent inputs, capacity or reactiontime. The general specifications for the Protrix® flow reactors aresummarised as follows; possible reaction types are, e.g. A+B→P1+Q (orC)→P, wherein the terms “A”, “B” and “C” represent educts, “P” and “P1”products, and “Q” quencher; throughput (ml/min) of from about 0.2 up toabout 20; channel dimensions (mm) of 1×1 (pre-heat and mixer zone),1.4×1.4 (residence channel); reagent feeds of 1 to 3; module dimensions(width×height) (mm) of 110×260; frame dimensions (width×height×length)(mm) approximately 400×300×250; number of modules/frame is one (minimum)up to four (max.). More technical information on the ChemtrixProtrix®reactor can be found in the brochure “CHEMTRIX—Scalable FlowChemistry—Technical Information Protrix®, published by Chemtrix BV in2017, which technical information is incorporated herein by reference inits entirety.

The Dow Corning as Type G1 SiC microreactor, which is scalable forindustrial production, and as well suitable for process development andsmall production can be characterized in terms of dimensions as follows:typical reactor size (length×width×height) of 88 cm×38 cm×72 cm; typicalfluidic module size of 188 mm×162 mm. The features of the Dow Corning asType G1 SiC microreactor can be summarized as follows: outstandingmixing and heat exchange: patented HEART design; small internal volume;high residence time; highly flexible and multipurpose; high chemicaldurability which makes it suitable for high pH compounds and especiallyhydrofluoric acid; hybrid glass/SiC solution for construction material;seamless scale-up with other advanced-flow reactors. Typicalspecifications of the Dow Corning as Type G1 SiC microreactor are asfollows: flow rate of from about 30 ml/min up to about 200 ml/min;operating temperature in the range of from about −60° C. up to about200° C., operating pressure up to about 18 barg (“barg” is a unit ofgauge pressure, i.e. pressure in bars above ambient or atmosphericpressure); materials used are silicon carbide, PFA (perfluoroalkoxyalkanes), perfluoroelastomer; fluidic module of 10 ml internal volume;options: regulatory authority certifications, e.g. FDA or EMA,respectively. The reactor configuration of Dow Corning as Type G1 SiCmicroreactor is characterized as multipurpose and configuration can becustomized. Injection points may be added anywhere on the said reactor.

Hastelloy® C is an alloy represented by the formula NiCr21Mo14W,alternatively also known as “alloy 22” or “Hastelloy® C-22. The saidalloy is well known as a highly corrosion resistantnickel-chromium-molybdenum-tungsten alloy and has excellent resistanceto oxidizing reducing and mixed acids. The said alloy is used in fluegas desulphurization plants, in the chemical industry, environmentalprotection systems, waste incineration plants, sewage plants. Apart fromthe before said example, in other embodiments of the invention, ingeneral nickel-chromium-molybdenum-tungsten alloy from othermanufactures, and as known to the skilled person, of course can beemployed in the present invention. A typical chemical composition (allin weight-%) of such nickel-chromium-molybdenum-tungsten alloy is, eachpercentage based on the total alloy composition as 100%: Ni (nickel) asthe main component (balance) of at least about 51.0%, e.g. in a range offrom about 51.0% to about 63.0%; Cr (chromium) in a range of from about20.0 to about 22.5%, Mo (molybdenum) in a range of from about 12.5 toabout 14.5%, W (tungsten or wolfram, respectively) in a range of fromabout 2.5 to about 3.5%; and Fe (iron) in an amount of up to about 6.0%,e.g. in a range of from about 1.0% to about 6.0%, preferably in a rangeof from about 1.5% to about 6.0%, more preferably in a range of fromabout 2.0% to about 6.0%. Optionally, the percentage based on the totalalloy composition as 100%, Co (cobalt) can be present in the alloy in anamount of up to about 2.5%, e.g. in a range of from about 0.1% to about2.5%. Optionally, the percentage based on the total alloy composition as100%, V (vanadium) can be present in the alloy in an amount of up toabout 0.35%, e.g. in a range of from about 0.1% to about 0,35%. Also,the percentage based on the total alloy composition as 100%, optionallylow amounts (i.e. ≤0.1%) of other element traces, e.g. independently ofC (carbon), Si (silicon), Mn (manganese), P (phosphor), and/or S(sulfur). In such case of low amounts (i.e. ≤0.1%) of other elements,the said elements e.g. of C (carbon), Si (silicon), Mn (manganese), P(phosphor), and/or S (sulfur), the percentage based on the total alloycomposition as 100%, each independently can be present in an amount ofup to about 0.1%, e.g. each independently in a range of from about 0.01to about 0.1%, preferably each independently in an amount of up to about0.08%, e.g. each independently in a range of from about 0.01 to about0.08%. For example, said elements e.g. of C (carbon), Si (silicon), Mn(manganese), P (phosphor), and/or S (sulfur), the percentage based onthe total alloy composition as 100%, each independently can be presentin an amount of, each value as an about value: C≤0.01%, Si≤0.08%,Mn≤0.05%, P≤0.015%, S≤0.02%. Normally, no traceable amounts of any ofthe following elements are found in the alloy compositions indicatedabove: Nb (niobium), Ti (titanium), Al (aluminum), Cu (copper), N(nitrogen), and Ce (cerium).

Hastelloy® C-276 alloy was the first wrought, nickel-chromium-molybdenummaterial to alleviate concerns over welding (by virtue of extremely lowcarbon and silicon contents). As such, it was widely accepted in thechemical process and associated industries, and now has a 50-year-oldtrack record of proven performance in a vast number of corrosivechemicals. Like other nickel alloys, it is ductile, easy to form andweld, and possesses exceptional resistance to stress corrosion crackingin chloride-bearing solutions (a form of degradation to which theaustenitic stainless steels are prone). With its high chromium andmolybdenum contents, it is able to withstand both oxidizing andnon-oxidizing acids, and exhibits outstanding resistance to pitting andcrevice attack in the presence of chlorides and other halides. Thenominal composition in weight-% is, based on the total composition as100%: Ni (nickel) 57% (balance); Co (cobalt) 2.5% (max.); Cr (chromium)16%; Mo (molybdenum) 16%; Fe (iron) 5%; W (tungsten or wolfram,respectively) 4%; further components in lower amounts can be Mn(manganese) up to 1% (max.); V (vanadium) up to 0.35% (max.); Si(silicon) up to 0.08% (max.); C (carbon) 0.01 (max.); Cu (copper) up to0.5% (max.).

In another embodiments of the invention, without being limited to, forexample, the microreactor suitable for the said production, preferablyfor the said industrial production, is an SiC-microreactor that iscomprising or is made only of SiC as the construction material (siliconcarbide; e.g. SiC as offered by Dow Corning as Type G1 SiC or byChemtrixMR555 Plantrix), e.g. providing a production capacity of fromabout 5 up to about 400 kg per hour.

It is of course possible according to the invention to use one or moremicroreactors, preferably one or more SiC-microreactors, in theproduction, preferably in the industrial production, of the fluorinatedproducts according to the invention. If more than one microreactor,preferably more than one SiC-microreactors, are used in the production,preferably in the industrial production, of the fluorinated productsaccording to the invention, then these microreactors, preferably theseSiC-microreactors, can be used in parallel and/or subsequentarrangements. For example, two, three, four, or more microreactors,preferably two, three, four, or more SiC-microreactors, can be used inparallel and/or subsequent arrangements.

For laboratory search, e.g. on applicable reaction and/or upscalingconditions, without being limited to, for example, as a microreactor thereactor type Plantrix of the company Chemtrix is suitable. Sometimes, ifgaskets of a microreactor are made out of other material than HDPTFE,leakage might occur quite soon after short time of operation because ofsome swelling, so HDPTFE gaskets secure long operating time ofmicroreactor and involved other equipment parts like settler anddistillation columns.

For example, an industrial flow reactor (“IFR”, e.g. Plantrix® MR555)comprises of SiC modules (e.g. 3M® SiC) housed within a (non-wetted)stainless steel frame, through which connection of feed lines andservice media are made using standard Swagelok fittings. The processfluids are heated or cooled within the modules using integrated heatexchangers, when used in conjunction with a service medium (thermalfluid or steam), and reacted in zig-zag or double zig-zag, meso-channelstructures that are designed to give plug flow and have a high heatexchange capacity. A basic IFR (e.g. Plantrix® MR555) system comprisesof one SiC module (e.g. 3M® SiC), a mixer (“MRX”) that affords access toA+B→P type reactions. Increasing the number of modules leads toincreased reaction times and/or system productivity. The addition of aquench Q/C module extends reaction types to A+B→P1+Q (or C)→P and ablanking plate gives two temperature zones. Herein the terms “A”, “B”and “C” represent educts, “P” and “P1” products, and “Q” quencher.

Typical dimensions of an industrial flow reactor (“IFR”, e.g. Plantrix®MR555) are, for example: channel dimensions in (mm) of 4×4 (“MRX”,mixer) and 5×5 (MRH-I/MRH-II; “MRH” denotes residence module); moduledimensions (width×height) of 200 mm×555 mm; frame dimensions(width×height) of 322 mm×811 mm. A typical throughput of an industrialflow reactor (“IFR”, e.g. Plantrix® MR555) is, for example, in the rangeof from about 50 l/h to about 400 l/h. in addition, depending on fluidproperties and process conditions used, the throughput of an industrialflow reactor (“IFR”, e.g. Plantrix® MR555), for example, can alsobe >400 l/h. The residence modules can be placed in series in order todeliver the required reaction volume or productivity. The number ofmodules that can be placed in series depends on the fluid properties andtargeted flow rate.

Typical operating or process conditions of an industrial flow reactor(“IFR”, e.g. Plantrix® MR555) are, for example: temperature range offrom about −30° C. to about 200° C.; temperature difference(service−process)<70° C.; reagent feeds of 1 to 3; maximum operatingpressure (service fluid) of about 5 bar at a temperature of about 200°C.; maximum operating pressure (process fluid) of about 25 bar at atemperature of about ≤200° C.

Use of a Fluorination Gas in Direct Fluorination:

In a particular embodiment, the present invention, in generally isdirected also to a use of a fluorination gas, wherein elemental fluorine(F₂) is present in a high concentration of substantially more than, inparticular very much more than 15% by volume or in particular than 20%by volume of elemental fluorine (F₂), especially of equal to much higherthan 25% by volume, i.e., at least 25% by volume, of elemental fluorine(F₂), preferably of equal to much higher than 35% by volume or inparticular than 45% by volume, for the manufacture of a fluorinatedcompound in a liquid medium comprising or consisting of a startingcompound having one or more hydrogen atoms that are capable of beingsubstituted by means of a halogenation reaction; preferably wherein thefluorine (F₂) is present in the fluorine containing gas in a highconcentration in a range of from 15-100% by volume, preferably within arange of from 20-100% by volume, more preferably within a range of from25-100% by volume, still more preferably within a range of from 30-100%by volume, even more preferably within a range of from 35-100% byvolume, an still more preferred within a range of from 45-100% byvolume, each based on the total volume of the fluorination gas as 100%by volume; with the proviso that the starting compound is not benzene,not benzoic acid, and not a benzoic acid derivative, and the fluorinatedcompound produced is not a fluorinated benzene, especially notmonofluorobenzene.

The following examples are intended to further illustrate the inventionwithout limiting its scope.

EXAMPLES

Following compounds or intermediates are prepared according to thisinvention:

Example 1

Reference to state of the art: U.S. Pat. No. 2,745,867, preparation overtrichloroacetonitrile followed by fluorination with HF with CrO3catalyst in gas phase to trifluoroacetonitrile

-   -   a) By electrochemistry: in U.S. Pat. No. 3,017,336 in a special        CN-containing electrolyte, carbon atom comes from anode        material→not industrial feasible.    -   b) Out of trifluoroacetic acid amide and P₂O₅ in CN 10274619.

Process of the Invention:

In a Batch fluorination counter-current apparatus having a pressurevalve at the top which is set to 20 bar and with a total volume of 10 l(see drawing 1), 4.0 kg (97.4 mol, 5.1 l) of absolute acetonitrile werefilled and the pump was started. The for the cooler a water cooling witha water temperature of 8° C. was used. When the temperature of theacetonitrile reached 15° C., the conc. F₂ valve was opened with a dosageof 20 mol F₂ gas/h. For this trial, the F₂-gas had a concentration of97%/h. Some purge gas leaves the apparatus together with slightlyoverdosed F₂. In total, 321.4 mol (6.11 kg) F₂ gas was fed over 5 h overa mass flow controller from Bronkhorst into the looping reactionmixture. Reaction samples were taken very carefully with a stainlesssteel cylinder (a sealed sampling system) after each hour. For analysis,the samples were hydrolyzed with same volume of water, the organic phasedried over Na₂SO₄ and injected into a Hewlett Packard Gas chromatographysystem. The sample taken after 5 h contained 96% CF₃CN.

(Batch) Work Up Procedure a)

The reaction mixture was fed slowly into water into a PTFE coatedsettler (tank with 20 bar), after decanting the water, the organic phasewas looped over a sieve with Na₂SO₄ for drying purpose and subjected toa fine distillation at 15 bar pressure in a stainless steel columncooled with −20° C. at the top cooler, all made out of 1.4771 high gradestainless steel. Over the top, a pre-fraction of CF₃CN together with HFleft first, afterwards 7.9 kg of pure CF₃CN (85% yield, 99.5% purity)could be obtained.

Continuous Work Up Procedure Using 2 Stainless Steel Columns b)

In said fluorination apparatus, a side stream taken after thecounter-current pump over a valve (valve bought from company Best) wascontinuously taken out the counter-current stream (stream back to thenozzles only little bit open) and is fed continuously into the middlepart of a stainless steel distillation column made out of 1.4571 steelwhich had a total volume of 2 liters. The pressure in the column is keptat 20 bar and the top condenser of the column is cooled with a coolingliquid down to −20° C. (reflux of liquid CF₃CN). As there are only smallamounts of CH₃CN present after reaction, the bottom of the column is notemptied at all but at the top boiler continuously CF₃CN is removed intoa stainless steel bottle staying in a cooling bath of CO₂. The isolatedyield after distillation was 89%.

Continuous distillation of CF₃CN out of synthesis with F₂. See FIG. 3.

The fluorination product can be used as raw material to prepare aconducting salt for lithium batteries.

Example 2

The fluorination of CH₃CN was repeated continuously in a microreactorsystem using in lab a 27 ml SiCmicroreactor from Chemtrix. The CH₃CN andF₂ feed was set to a molar ratio of 1:3.1 and the reactor was kept at 5°C. The liquid feed was 234 g (5.7 mol, 300 ml) CH₃CN per hour. TheF₂-gas stream, which come directly from a fluorine electrolysis cell(controlled with a Bronkhorst mass flow meter), was fed together withthe CH₃CN in a split and re-combine system before it entered into themicroreactor channels. The achieved yield after continuous 2 columndistillation like described in example 1 gave a CF₃CN yield of 96%.

Example 3

Methane sulfonic acid fluoride was fluorinated in batch at 10° C.according to Example 1. The yield was 78% after a continuous finedistillation.

The fluorination product trifluoromethane sulfonyl fluoride (TFSAF)gives triflic acid after hydrolysis or can be used as raw material toprepare LiTFSI (Li-salt of1,1,1-trifluoro-N-[(trifluoromethyl)sulfonyl]-methanesulfonamide).

Example 4

The fluorination of methane sulfonic acid fluoride was done in a 27 mlSiCmicroreactor (see Example 2). The achieved yield was 98%.

Example 5

The fluorination was done in a microreactor system at 10° C. (seeExample 2). The achieved yield was 94%.

Example 6

Preparation of F—CN (Analogous to Cl—CN):

In the prior art Cl—CN is described by synthesis with C12 to give Cl—CN;see for example, WO 2014/065422 and Maugin, Ch.; Simon, L.-J., in Annalidi ChimicaApplicata (1921)15, 18-41). F—CN is only described in theprior art by synthesis out of Cl—CN by Seel, Fritz; Ballreich, Kurt inChemischeBerichte (1959)92, 344-6 or 2,4,6-Trifluoro-s-triazine by Wu,Y.-Q. in Science of Synthesis (2005)18, 17-63).

Process according to the invention:

Advantage here is a very high purity of the bis-fluorosulfonyl imide asthe fluorine atom is in the molecule before formation of the amide.Fluorination of any chlorosulfonylbis-amide also gives thebis-fluorosulfonyl imide but all fluorinating agents and fluorinationmethods leave impurities which cannot or only be removed with muchefforts. Very high purities are needed for usage as conducting salt inbattery electrolytes.

The fluorination product can be used as raw material to prepare aconducting salt for lithium batteries.

Example 7

Synthesis of NF3 NF3 is prepared out of F₂ and N-Plasma like in U.S.Pat. No. 3,961,024 without catalyst or metal fluoride catalyst or likein U.S. Pat. No. 3,304,248, or out of NH₃ and F₂ under Cu catalysis likein U.S. Pat. No. 3,214,237 or even out of C—F compounds like in U.S.Pat. No. 3,043,662 or in newer applications out of NH₄×HF and F₂ gaslike in U.S. Pat. No. 4,091,081, JP 55008926 and JP 03236487. All knownmethods are either very difficult to perform and even dangerous(strongly oxidizing materials to handle), have low yield and or highenergy consumption like in DE 3722163, JP 04131391 and CN 103896223 inthe synthesis by electrolysis or in special apparatus like in JP02255512. Very often, due to safety, additional gases like CF₄ andothers are either added like in JP 02255513. In electrolysis, mostalways much CF₄ is formed in situ out of carbon electrode material. ThisCF₄ must be removed for commercial applications. This inventiondiscloses the safe synthesis of NF₃ out of NH₃ and/or H2N—NH₂ usingconcentrated F₂ gas in micoreactors and the preparation of a technicalgrade material. Besides safety this procedure has the advantage that NOCF₄ is formed which finally leads to a less challenging purification.Semiconductor grade material can be made e.g. according to WO2017138366, KR 2017023281, CN 106276828, CN 103896224 and many otherprocedures.

Inventive: Continuous synthesis of NF₃ in microreactor.

In the microreactor apparatus as given in FIG. 2 (see also Example 2),3.01 mol/h high concentrated F₂ gas from F₂ production electrolysis(over a Bronkhorst flow meter) was fed together with 1 mol/h NH₃ from aNH₃ tank into a 27 ml SiCmicroreactor from Chemtrix at 60° C. A secondmicroreactor was added in series just to extend residence time and tohave a better temperature and pressure control for the reaction. Theleaving material was collected in a stainless steel cylinder cooled byliquid nitrogen.

Example 8

Conversion of Tetrafluorohydrazine N₂F₄ to NF₃

N₂F₄ can be co-produced respectively is formed as side product byexisting electrolysis plants to make NF₃ out of NH₄F×HF by electrolysis.Also the conversion of this N₂F₄ containing already larger amounts ofNF₃ is included into this invention as a purification step usingmicroreactor technology which is easier than e.g. absorption methods asdescribed in EP 366078 or JP 03208806.

The amount of F₂ fed into the microreactor at parameters like in Example7 (see also FIG. 2) is 5% above the N₂F₄ content. In an typical example,90% NF₃/10% N₂F₄ containing gas was fed into a microreactor togetherwith F₂. The leaving material contained no N₂F₄ anymore.

Example 9

Converson of Difluorodiazine N₂F₂ to NF₃.

N₂F₂ also can be a side product in NF₃ preparation processes and can bepurified by using microreactor technology.

5% N₂F₂ containing NF₃ gas was treated with conc. F₂ in a microreactor(see also FIG. 2, and Example 2). No N₂F₂ could be detected any moreafter the reactor.

Example 10

Purification of NF₃ out of example 7 (−9) to a technical grade product.

In 2 stainless steel columns NF₃ and HF as achieved in example 7 werefed continuously into a 2 stainless steel column apparatus having 2 lvolume each in the bottom. For a stable pressure and a continuous feedinto the columns a membrane compressor either directly added after themicroreactor or connected to the stainless steel cylinder withpreviously collected crude material was used. At 50 bar pressure and aNF₃ reflux at −30° C., a 99.9 technical grade NF₃ was continuouslycollected. HF is isolated at the top of a second column as illustratedbelow. This is a general method to purify NF₃ also product produced byelectrolysis from which the tars in the bottom of the second columncomes from.

Continuous distillation of NF₃ crude material out of synthesis with highconc. F₂. See FIG. 4.

Example 11

Synthesis of Monofluoromalonate.

Direct fluorination was described already out of the Na-salts and bydirect fluorination or even out of diazomalonate, both known procedures,however, are more sophisticated than inventive method hereunder.

The fluorination of methylmalonate was done continuously in amicroreactor system using in lab a 27 ml SiCmicroreactor from Chemtrix(see also FIG. 2, and Example 2). The malonate/F₂ feed was set to amolar ratio of 1 to 1.01 and the reactor was kept at 5° C. The liquidfeed was 200 g (1.51 mol) Malonate per hour. The F₂-gas stream, whichcomes directly from a fluorine electrolysis cell (controlled with aBronkhorst mass flow meter), was fed together with the malonate into asplit and re-combine system before it entered into the microreactorchannels but a trial without that premixer showed almost same results.Samples for reaction control were taken and just slowly hydrolyzed intoice water to get rid of HF, the organic phase directly injected into GC(gas choromatography) without further purification and without drying.All material leaving the microreactor were collected in a reservoir witha small condenser, collected material was kept at 0° C. Themonofluoromalonate was obtained in pure form (90% purity) and a yield of94% after fine distillation (bp: 111° C.) over a stainless steel column(10 cm length, filled with 10 mm Raschig Rings of PE) at atmosphericpressure.

Example 12

Continuous Purification of FluoromalonateRaw Material.

In two stainless steel columns in series (see also FIG. 1, and Example1), the raw material out of trial 11 was fed continuously into the firstcolumn separating the HF at 21° C. at the top of the first column. Thebottom HF free material containing some impurities and thefluorolalonate was fed into the second column yielding the purefluoromalonate at the top of the second column at 11° C. 94% of the massfed into this distillation system could be re-collected.

Example 13

Reaction of 1,3-Dinitrobenzene with Highly Concentrated F₂.

In the microreactor apparatus system as given herein (see also FIG. 2)with two 27 ml microreactors from Chemtrix, 104.5 g/h (2.75 mol/h) highconcentrated F₂ gas from F₂ production electrolysis (over a Bronkhorstflow meter) was fed together with 470.7 g/h (2.8 mol/h)1,3-dinitro-benzene in CH₃CN from a storage reservoir (tank), bothmicroreactors were heated to 70° C., the pressure was adjusted at 2 barabsolute by a pressure valve after the second microreactor (the secondmicroreactor in series is just to extend residence time and to have abetter temperature and pressure control for the reaction). The leavingmaterial after the pressure valve was collected in a cooled stainlesssteel cylinder followed by a scrubber where the material coming from themicroreactors enters the cylinder over a deep pipe. Workup was done byfeeding the product mixture into ice water to remove the HF. The organicphase was analyzed by GC-MS and showed no starting material. A finedistillation of the organic phase (after removing the solvent CH₃CN at arotavapor) at 0.01 mbar and a condenser temperature of 30° C. delivered1-fluoro-2,4-dinitro-benzene at 149° C. transition temperature. At 20°C., the distilled material became crystalline. The isolated yield wasabout 89% of theory (about 455 g) in one hour of reaction time.

Example 14

Reaction of 3-Nitro-benzonitrile with Highly Concentrated F₂.

In the microreactor apparatus system as given herein (see also FIG. 2)with two 27 ml microreactors from Chemtrix, 100.0 g/h (2.63 mol/h)highly concentrated F₂ gas from F₂ production electrolysis (over aBronkhorst flow meter) was fed together with 399.9 g/h (2.7 mol/h)3-nitro-benzonitrile in CH₃CN from a storage reservoir (tank), bothmicroreactors were heated to 90° C., the pressure was adjusted at 2 barabsolute by a pressure valve after the second microreactor (the secondmicroreactor in series is just to extend residence time and to have abetter temperature and pressure control for the reaction). The leavingmaterial after the pressure valve was collected in a cooled stainlesssteel cylinder followed by a scrubber where the material coming from themicroreactors enters the cylinder over a deep pipe. Workup was done byfeeding the product mixture into ice water to remove the HF. The organicphase was analyzed by GC-MS and showed only traces of starting material.The solvent was removed at a rotavapor and the residue distilled at 0.01mbar at a transition temperature of 155° C., giving about 345 g (about79% of theory) of 3-fluoro-5-nitro-benzonitrile, in one hour of reactiontime.

What is claimed is:
 1. A process for the manufacture of a fluorinatedcompound by direct fluorination, wherein the process comprises the stepsof: a) provision of a liquid medium comprising or consisting of astarting compound having one or more hydrogen atoms that are capable ofbeing substituted by means of a halogenation reaction; b) provision of afluorination gas comprising or consisting of elemental fluorine (F₂),wherein the fluorine is present in the fluorination gas in a highconcentration of at least substantially more than, in particular verymuch more than 15% by volume (vol.-%), preferably equal to or more than20% by volume (vol.-%); c) provision of a reactor or reactor system,resistant to elemental fluorine (F₂) and hydrogen fluoride (HF); d)passing the fluorination gas of b), in a reactor or reactor system ofc), through the liquid medium of a) comprising or consisting of thestarting compound, and thereby reacting the starting compound with theelemental fluorine (F₂) to substitute in the starting compound at leastone of the one or more hydrogen atoms for fluorine, and wherein thereaction is carried out at temperature of from about −30° C. to about+100° C. and a pressure of from about 1 bar absolute bar to about 20 barabsolute bar; e) withdrawing the fluorinated compound formed in step d)from the reactor or reactor system of c); f) to obtain a fluorinatedcompound wherein at least one of the one or more hydrogen atoms of thestarting compound is replaced by fluorine atom; with the proviso thatthe starting compound is not benzene, not benzoic acid, and not abenzoic acid derivative, and the fluorinated compound produced is not afluorinated benzene, especially not monofluorobenzene.
 2. The processfor the manufacture of a fluorinated compound according to claim 1,wherein the elemental fluorine (F₂) is present in the fluorination gasof b) in a high concentration of at least 25% by volume, preferably ofat least 30% by volume, more preferably of at least 35% by volume, evenmore preferably of at least 45% by volume, each based on the totalvolume of the fluorination gas as 100% by volume.
 3. The process for themanufacture of a fluorinated compound according to claim 2, wherein thefluorine (F₂) is present in the fluorination gas of b) in a highconcentration within a range of from 15-100% by volume, preferablywithin a range of from 20-100% by volume, more preferably within a rangeof from 25-100% by volume, still more preferably within a range of from30-100% by volume, even more preferably within a range of from 35-100%by volume, an still more preferred within a range of from 45-100% byvolume, each based on the total volume of the fluorination gas as 100%by volume.
 4. The process for the manufacture of a fluorinated compoundaccording to claim 1, wherein the starting compound is an inorganicstarting compound, preferably an inorganic starting compound selectedfrom the group consisting of ammonia, hydrogen cyanide, hydrazine,tetrafluorohydrazine, difluorodiazine, sulphur hexafluoride (SF₆), andiodine pentafluoride (IF₅).
 5. The process for the manufacture of afluorinated compound according to claim 1, wherein the compound is anorganic starting compound, but is not benzene, preferably wherein thestarting compound is an organic starting compound selected from thegroup consisting of acetonitrile, monofluoro acetonitrile,difluoroacetonitrile, methane sulfonic acid fluoride, monofluoromethanesulfonic acid fluoride, difluoromethane sulfonic acid fluoride, methanesulfonic acid fluoride, ethylene carbonate, monofluoroethylenecarbonate, difluoroethylene carbonate, trifluoroethylene carbonate,formaldehyde (H2C═O), difluorophosgene (F₂C═O), 2,2,2-trifluoroethylmethyl ether, acetic acid ethyl ether, monofluoroacetic acid ethylether, difluoroacetic acid ethyl ether, methyl acrylate, a malonic aciddiester starting compound, preferably malonic acid dimethyl ester, a1,3-dicarbonyl methylene starting compound, a C6-aromatic compound, butnot benzene, a deactivated benzene derivative, a C10-aromatic compound,a deactivated C10-aromatic compound, a 5-membered heterocyclic compound,a 6-membered heterocylic compound, a 5-membered heteroaromatic compound,a 6-membered heteroaromatic compound, preferably pyridine, uracil, andcytosine.
 6. The process for the manufacture of a fluorinated compoundaccording to claim 1, wherein the reaction is carried out in a(closed)column reactor, wherein the liquid medium of a) comprising orconsisting of the starting compound is circulated in a loop, while thefluorination gas of b) comprising or consisting of elemental fluorine(F₂) in a high concentration is fed into the column reactor of c) and instep d) is passed through the liquid medium to react with the startingcompound; preferably wherein the loop is operated with a circulationvelocity of from 1,500 l/h to 5,000 l/h, more preferably of from 3,500l/h to 4,500 l/h.
 7. The process for the manufacture of a fluorinatedcompound according to claim 6, wherein the column reactor is equippedwith at least one of the following: (i) at least one cooler (system), atleast one liquid reservoir, with inlet and outlet for, and containingthe liquid medium of a) comprising or consisting of an inorganiccompound or organic compound as the starting compound; (ii) a pump forpumping and circulating the liquid medium of a); (iii) one or more(nozzle) jets, preferably wherein the one or more (nozzle) jets areplaced at the top of the column reactor, for spraying the circulatingmedium of a) into the column reactor; (iv) one or more feeding inletsfor introducing the fluorination gas of b) comprising or consisting ofelemental fluorine (F₂) in a high concentration into the column reactor;(v) optionally one or more sieves, preferably two sieves, preferably theone or more sieves placed at the bottom of the column reactor; (vi) andat least one gas outlet equipped with a pressure valve, and at least oneoutlet for withdrawing the fluorinated inorganic compound or organiccompound in step e).
 8. The process for the manufacture of a fluorinatedcompound according to claim 6, wherein column reactor is a packed bedtower reactor, preferably a packed bed tower reactor which is packedwith fillers resistant to elemental fluorine (F₂) and hydrogen fluoride(HF), e.g. with Raschig fillers and/or metal fillers, more preferablywherein the packed bed tower reactor is a gas scrubber system (tower)which is packed with fillers resistant to elemental fluorine (F₂) andhydrogen fluoride (HF), e.g. Raschig fillers and/or metal fillers. 9.The process for the manufacture of a fluorinated compound according toclaim 6, wherein the reaction is carried out with a counter-current flowof the circulating liquid medium of a) comprising or consisting of thestarting compound and of the fluorination gas of b) fed into the columnreactor and which fluorination gas of b) is comprising or consisting ofelemental fluorine (F₂) in a high concentration.
 10. The process for themanufacture of a fluorinated compound according to claim 1, wherein thereaction is carried out in at least one step as a continuous processes,wherein the continuous process is performed in at least one continuousflow reactor with upper lateral dimensions of about ≤5 mm, or of about≤4 mm, preferably in at least one microreactor; more preferably whereinof the said steps at least (b2) the step of a fluorination reaction is acontinuous process in at least one microreactor under one or more of thefollowing conditions: flow rate: of from about 10 ml/h up to about4001/h; temperature: of from about 30° C. up to about 150° C.; pressure:of from about 4 bar up to about 50 bar; residence time: of from about 1second, preferably from about 1 minute, up to about 60 minutes.
 11. Theprocess of preparing a compound according to claim 10, wherein at leastone of the said continuous flow reactors, preferably at least one of themicroreactors, independently is a SiC-continuous flow reactor,preferably independently is an SiC-microreactor.
 12. A use of afluorination gas, wherein elemental fluorine (F₂) is present in a highconcentration of substantially more than, in particular very much morethan 15% by volume or in particular than 20% by volume of elementalfluorine (F₂), especially of equal to much higher than 25% by volume,i.e., at least 25% by volume, of elemental fluorine (F₂), preferably ofequal to much higher than 35% by volume or in particular than 45% byvolume, for the manufacture of a fluorinated compound in a liquid mediumcomprising or consisting of a starting compound having one or morehydrogen atoms that are capable of being substituted by means of ahalogenation reaction; preferably wherein the fluorine (F₂) is presentin the fluorine containing gas in a high concentration in a range offrom 15-100% by volume, preferably within a range of from 20-100% byvolume, more preferably within a range of from 25-100% by volume, stillmore preferably within a range of from 30-100% by volume, even morepreferably within a range of from 35-100% by volume, an still morepreferred within a range of from 45-100% by volume, each based on thetotal volume of the fluorination gas as 100% by volume; with the provisothat the starting compound is not benzene, not benzoic acid, and not abenzoic acid derivative, and the fluorinated compound produced is not afluorinated benzene, especially not monofluorobenzene.